Ocular Transporters in Ophthalmic Diseases and Drug Delivery (Ophthalmology Research)

This exceptionally important new work represents recent discoveries and advancements in the study of ocular transporters and their roles in ocular physiology, pathology, and drug delivery. Transporters are found on the membranes of cells and play a key role in transmitting signals between cells. In Ocular Transporters in Ophthalmic Diseases and Drug Delivery, a panel of distinguished authors discusses all the latest developments in the study of ocular transporters. Focusing on the molecular characteristics, localization, and substrate specificities in various compartments of the eye, this volume discusses how transporters regulate the clarity of the cornea and lens,В the movements of fluids across the ciliary epithelium, and the transport of nutrients across the retinal pigment epithelium. It also provides an in-depth look at how mutations or dysfunction of specific transporters can contribute to various disorders in the eye, including blindness, and provides readers with potential targets and strategies to allow safe passage of therapeutic drugs into the eye. Ocular Transporters in Ophthalmic Diseases and Drug Delivery is the first text book in this field and offers up-to-date information to clinicians, research scientists in academia, and the pharmaceutical industry. This work has clinical implications for drug development and therapeutic drug delivery, making it an invaluable resource for readers. 1 1 -- Alan S. Verkman -- 2 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 -- Nigel L. Barnett and Natalie D. Bull -- 19 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 -- Nigel L. Barnett and Natalie D. Bull -- 19 -- Erica L. Fletcher and Michelle M. Ward -- 20 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 -- Nigel L. Barnett and Natalie D. Bull -- 19 -- Erica L. Fletcher and Michelle M. Ward -- 20 -- Mayssa Attar and Jie Shen -- 21 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 -- Nigel L. Barnett and Natalie D. Bull -- 19 -- Erica L. Fletcher and Michelle M. Ward -- 20 -- Mayssa Attar and Jie Shen -- 21 -- Sriram Gunda, Sudharshan Hariharan, Nanda Mandava, and Ashim K. Mitra -- 22 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 -- Nigel L. Barnett and Natalie D. Bull -- 19 -- Erica L. Fletcher and Michelle M. Ward -- 20 -- Mayssa Attar and Jie Shen -- 21 -- Sriram Gunda, Sudharshan Hariharan, Nanda Mandava, and Ashim K. Mitra -- 22 -- Swita Raghava, Gaurav Goel, and Uday B. Kompella -- 23 1 -- Alan S. Verkman -- 2 -- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny -- 3 -- Ram Kannan and Hovhannes J. Gukasyan -- 4 -- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To -- 5 -- Paul J. Donaldson and Julie Lim -- 6 -- Nicholas A. Delamere and Shigeo Tamiya -- 7 -- Donald G. Puro -- 8 -- Masatoshi Tomi and Ken-ichi Hosoya -- 9 -- Adnan Dibas and Thomas Yorio -- 10 -- Lawrence J. Rizzolo -- 11 -- Olaf Strauss -- 12 -- Ali A. Hussain and John Marshall -- 13 -- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott -- 14 -- Paul P.M Schnetkamp et al -- 15 -- Vijay Sarthy and David Pow -- 16 -- Giovanni Casini -- 17 -- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases / -- Esther E. Biswas-Fiss -- 18 -- Nigel L. Barnett and Natalie D. Bull -- 19 -- Erica L. Fletcher and Michelle M. Ward -- 20 -- Mayssa Attar and Jie Shen -- 21 -- Sriram Gunda, Sudharshan Hariharan, Nanda Mandava, and Ashim K. Mitra -- 22 -- Swita Raghava, Gaurav Goel, and Uday B. Kompella -- 23 -- Vadivel Ganapathy, Sudha Ananth, Sylvia B. Smith, and Pamela M. Martin -- 24 1-- Alan S. Verkman-- 2-- Peter S. Reinach, José E. Capó-Aponte, Stefan Mergler, and Kathryn S. Pokorny-- 3-- Ram Kannan and Hovhannes J. Gukasyan-- 4-- Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, and Chi-ho To-- 5-- Paul J. Donaldson and Julie Lim-- 6-- Nicholas A. Delamere and Shigeo Tamiya-- 7-- Donald G. Puro-- 8-- Masatoshi Tomi and Ken-ichi Hosoya-- 9-- Adnan Dibas and Thomas Yorio-- 10-- Lawrence J. Rizzolo-- 11-- Olaf Strauss-- 12-- Ali A. Hussain and John Marshall-- 13-- Paul A. Constable, John G. Lawrenson, and N. Joan Abbott-- 14-- Paul P.M Schnetkamp et al-- 15-- Vijay Sarthy and David Pow-- 16-- Giovanni Casini-- 17-- Biochemical defects associated with genetic mutations in the retina-specific ABC transporter, ABCR, and macular degenerative diseases /-- Esther E. Biswas-Fiss-- 18-- Nigel L. Barnett and Natalie D. Bull-- 19-- Erica L. Fletcher and Michelle M. Ward-- 20-- Mayssa Attar and Jie Shen-- 21-- Sriram Gunda, Sudharshan Hariharan, Nanda Mandava, and Ashim K. Mitra-- 22-- Swita Raghava, Gaurav Goel, and Uday B. Kompella-- 23-- Vadivel Ganapathy, Sudha Ananth, Sylvia B. Smith, and Pamela M. Martin-- 24-- Jorge Fischbarg. cover-large.gif.jpg......Page 1 front-matter.pdf......Page 2 INTRODUCTION......Page 17 AQUAPORIN EXPRESSION IN OCULAR TISSUES–INDIRECT EVIDENCE FOR A ROLE IN EYE PHYSIOLOGY......Page 18 ROLES OF AQUAPORINS IN MAMMALIAN PHYSIOLOGY DEDUCED FROM PHENOTYPES OF AQP-NULL MICE......Page 19 Aquaporin 1 and Cataract Formation......Page 21 Aquaporin 1 in Corneal Endothelium – its Role in Corneal Transparency......Page 22 Aquaporins and Ocular Surface Fluid Secretion......Page 24 Aquaporin 3 and Healing of Corneal Epithelial Wounds......Page 25 SUMMARY AND PERSPECTIVE......Page 27 REFERENCES......Page 28 OVERVIEW......Page 31 INVOLVEMENT OF ION TRANSPORT MECHANISMS IN MEDIATED RECEPTOR CONTROL OF CORNEAL EPITHELIAL CELL RENEWAL AND VOLUME REGULATION......Page 33 Na+/K+-Adenosine Triphosphatase (ATPase) and Na:K:2Cl Cotransporter......Page 36 K+/Cl- Cotransporter......Page 39 Na+/H+ and Cl-/HCO - Exchangers......Page 40 Plasma Membrane and Endoplasmic Reticulum (ER) Ca2+ Pumps......Page 41 Organic Ion Transporters......Page 42 K+ Channels......Page 46 Cl- Channels......Page 47 Voltage-Dependent Ca2+ Channels......Page 48 TRP Channels......Page 51 REFERENCES......Page 53 Function......Page 61 Transport......Page 62 Function......Page 63 Transport......Page 64 OCULAR SURFACE AND TEAR FILM......Page 65 FUTURE DIRECTIONS......Page 66 REFERENCES......Page 67 INTRODUCTION......Page 72 POSSIBLE MECHANISMS FOR THE SECRETION OF AQUEOUS HUMOR......Page 73 NA+ SECRETION......Page 74 HCO - SECRETION......Page 77 Na+-K+-2Cl- Symport Versus Parallel Cl-/HCO - and Na+/H+ Antiports......Page 79 Cl- Release from NPE Cells into the Posterior Chamber......Page 81 At the Stromal Surface of PE Cells......Page 83 Cyclic AMP......Page 84 A3 Adenosine Receptors (A3ARs)......Page 85 Nitric Oxide......Page 86 REFERENCES......Page 87 INTRODUCTION......Page 98 LENS STRUCTURE AND FUNCTION......Page 99 DIFFERENTIAL EXPRESSION OF MEMBRANE TRANSPORTERS IN THE LENS......Page 100 Diabetic Cataract: a Problem with Lens-Volume Regulation?......Page 105 Age-Related Nuclear (ARN) Cataract - a Transport Problem?......Page 110 Differential Expression of Nutrient Transporters in the Lens......Page 111 Nutrient Delivery to the Lens Nucleus via the Sutures......Page 113 A Model for Age-Related Nuclear Cataract......Page 114 REFERENCES......Page 115 SUMMARY......Page 120 NA, K-ATPASE DISTRIBUTION IN THE LENS......Page 121 LENS NA, K-ATPASE TURNOVER......Page 123 REGULATION OF LENS NA, K-ATPASE ACTIVITY......Page 125 LENS OSMOREGULATION AND OPACIFICATION......Page 126 REFERENCES......Page 130 PERICYTES AND CAPILLARY FUNCTION......Page 133 FUNCTIONAL SPECIALIZATIONS OF THE RETINAL MICROVASCULATURE......Page 134 EFFECTS OF DIABETES ON MICROVASCULAR KIR CHANNELS......Page 135 HYPERGLYCEMIA AND PERICYTE CHANNELS......Page 137 BREAKDOWN OF THE BLOOD–RETINAL BARRIER AND ION CHANNEL FUNCTION......Page 138 METABOLIC MODULATION OF MICROVASCULAR FUNCTION......Page 139 REFERENCES......Page 140 INTRODUCTION......Page 144 Glucose......Page 146 Lactate......Page 147 ANTIOXIDANT SUPPLY......Page 148 Cystine......Page 149 Leucine......Page 151 ADENOSINE TRANSPORT......Page 153 ATP-BINDING CASSETTE (ABC) TRANSPORTERS......Page 154 REFERENCES......Page 156 Regulation of Transport in the RPE......Page 160 TRANSPORT OF NUTRIENTS AND IONS FROM THE SUBRETINAL SPACE TO THE CHORIOCAPILLARIS......Page 161 MECHANISM OF TRANSPORT OF IONS IN RETINAL PIGMENT EPITHELIUM......Page 162 K+ AND Na+ CHANNELS......Page 166 Cyclic AMP-activated Cystic-Fibrosis Transmembrane Regulator (CFTR) Channels......Page 168 Calcium-Activated Cl Channels (CACL or CaCC)......Page 169 ELECTRONEUTRAL CATION-Cl- COTRANSPORTERS (SLC12)......Page 170 REGULATION OF [Cl-]I AND THE RELATIONSHIP WITH BICARBONATE TRANSPORTERS......Page 171 BICARBONATE TRANSPORTERS IN RETINAL PIGMENT EPITHELIUM AND FUNCTIONAL COUPLING TO OTHER RETINAL CELL LAYERS......Page 172 CARBONIC ANHYDRASES......Page 173 MONOCARBOXYLATE TRANSPORTERS (MCT)......Page 174 AQP1, AQP9 AND EDEMA......Page 175 BUFFERING OF IONS IN THE SUBRETINAL SPACE IN THE LIGHT-DARK CYCLE AND EXPLANATION OF ELECTRORETINOGRAM (ERG) C-WAVE AND DELAYED HYPERPOLARIZATION......Page 177 OTHER IMPORTANT RETINAL PIGMENT EPITHELIUM TRANSPORT MECHANISMS......Page 178 ACKNOWLEDGEMENTS......Page 179 REFERENCES......Page 180 SUMMARY......Page 188 PROPERTIES OF GLUCOSE TRANSPORTERS......Page 189 STRUCTURE OF THE OUTER BLOOD–RETINAL BARRIER......Page 190 Development of Tight Junctions in Chick Retinal Pigment Epithelium......Page 192 Expression of Glucose Transporters In Vivo......Page 194 Effect of the Neural Retina on the Expression of Glucose Transporters......Page 196 REFERENCES......Page 198 Ca2+-REGULATED FUNCTIONS OF THE RETINAL PIGMENT EPITHELIUM......Page 203 Voltage-Dependent Ca2+ Channels......Page 206 The Functional Role of Neuroendocrine L-Type Ca2+Channels in the Retinal Pigment Epithelium......Page 207 L-type Channels and Disease in the Retinal Pigment Epithelium......Page 209 TRP Channels......Page 210 SUMMARY......Page 211 REFERENCES......Page 212 INTRODUCTION......Page 219 FUNCTIONAL IMPORTANCE OF TAURINE IN THE RETINA......Page 220 TRANSPORT PATHWAYS FOR DELIVERY OF RETINAL TAURINE......Page 222 Taurine Transport by Retinal Pigment Epithelium......Page 224 AGEING OF THE TAURINE TRANSPORT SYSTEM: IMPLICATIONS FOR DISEASE......Page 226 CONCLUSIONS......Page 231 REFERENCES......Page 232 THE RETINAL PIGMENT EPITHELIUM......Page 236 P-GLYCOPROTEIN STRUCTURE......Page 237 P-GLYCOPROTEIN SUBSTRATES......Page 239 Inhibition of P-glycoprotein......Page 242 LOCALIZATION OF P-GLYCOPROTEIN IN THE RETINAL PIGMENT EPITHELIUM......Page 243 OCULAR SIDE-EFFECTS OF DRUGS......Page 244 DRUG DELIVERY......Page 245 REFERENCES......Page 246 INTRODUCTION......Page 255 Functional and Molecular Properties of the Rod Outer Segment Na+/Ca2+-K+ Exchanger......Page 256 Regulation of the Rod Na+/Ca2+-K+ Exchanger......Page 257 Interaction of the Na+/Ca2+-K+ Exchanger with other ROS Proteins......Page 258 Cloning and Analysis of Rod NCKX1 cDNAs......Page 259 Cloning and Analysis of a Second Retinal NCKX cDNA......Page 260 Post-translational Modification: Alternative Splicing, N-terminal Signal-peptide Cleavage and Glycosylation of NCKX1 and NCKX2......Page 261 Residues Important for Cation Transport......Page 264 Membrane Topology and Helix Packing of the NCKX2 Protein......Page 266 CONCLUSIONS......Page 267 REFERENCES......Page 268 INTRODUCTION......Page 272 EXCITATORY AMINO ACID TRANSPORTER (EAAT) LOCALIZATION......Page 273 DEVELOPMENTAL EXPRESSION......Page 276 Role in Synaptic Transmission......Page 277 Role in Gamma Aminobutyric Acid (GABA) Synthesis......Page 278 Interacting Proteins......Page 279 Excitatory Amino Acid Transporter Trafficking......Page 280 System N Transporters......Page 281 System L Transporters......Page 282 DISEASE INVOLVEMENT......Page 283 ACKNOWLEDGEMENTS......Page 284 REFERENCES......Page 285 SUMMARY......Page 290 NEUROTRANSMITTER TRANSPORTERS......Page 291 GABA TRANSPORTERS......Page 292 THE GABAERGIC SYSTEM IN THE RETINA......Page 293 GABA UPTAKE AND TRANSPORTERS IN THE RETINA......Page 295 GAT-1 in Ganglion Cells and/or Displaced Amacrine Cells......Page 296 GAT-1 in Amacrine Cells......Page 297 GAT-1 in Bipolar Cells......Page 300 GAT-1 in Horizontal Cells......Page 301 Summary of the Localization of GAT-1 in the Retina......Page 302 Regulation of GABA Receptor Activation by GAT-1 at Retinal Synapses......Page 303 GAT-1 and Retinal Development......Page 304 REFERENCES......Page 305 INTRODUCTION......Page 311 ABCR IS A MEMBER OF THE ATP BINDING CASSETTE (ABC) TRANSPORTER FAMILY......Page 312 CELLULAR TRANSPORT FUNCTION IN ABCR......Page 313 PROTEIN DOMAINS OF ABCR AND THEIR FUNCTIONS......Page 315 THE NUCLEOTIDE BINDING DOMAINS OF ABCR.......Page 316 ABCR-RELATED DEGENERATIVE MACULOPATHIES REPRESENT COMPLEX ETIOLOGIES: POTENTIAL DIRECTIONS FOR FUTURE RESEARCH......Page 317 REFERENCES......Page 319 GLUTAMATE TRANSPORTERS......Page 327 EAAT1......Page 328 EAAT5......Page 329 Ischemia......Page 330 Glaucoma......Page 332 Retinitis Pigmentosa......Page 333 Protein Kinases and Phosphatases......Page 334 Soluble factors......Page 336 Transporter Substrates......Page 338 ACKNOWLEDGMENTS......Page 339 REFERENCES......Page 340 INTRODUCTION......Page 348 THE IMPORTANCE OF GLUTAMATE TRANSPORT......Page 349 Excitatory Amino Acid Transporters in the Retina......Page 350 CHANGES IN GLUTAMATE HOMEOSTASIS IN THE RETINA DURING DIABETES......Page 355 MECHANISMS INVOLVED IN ALTERED GLUTAMATE FUNCTION......Page 358 Neuronal Dysfunction and Cell Death......Page 359 Abnormalities in Glutamate Transport as a Generalized Indicator of Müller Cell Dysfunction......Page 360 REFERENCES......Page 361 INTRODUCTION......Page 365 The Ocular Surface......Page 366 The Back of the Eye......Page 368 ENZYME DISTRIBUTION IN OCULAR TISSUES......Page 369 Cytochrome P450 Enzymes in the Eye......Page 370 Hydrolytic Enzymes......Page 371 Polymorphism......Page 372 Inhibition......Page 373 Induction......Page 374 Transporters......Page 375 Neurodegeneration......Page 376 DRUG TRANSPORTER–METABOLIC ENZYME INTERPLAY......Page 377 REFERENCES......Page 380 INTRODUCTION......Page 388 Cornea......Page 390 Bowman’s Layer......Page 391 Conjunctiva......Page 392 Posterior Segment......Page 393 Retinal Vessels......Page 394 Retinal Pigment Epithelium......Page 395 PHYSICOCHEMICAL PROPERTIES OF DRUGS AFFECTING PERMEABILITY ACROSS OCULAR BARRIERS......Page 396 EFFLUX PUMPS......Page 397 P-Glycoprotein......Page 398 REFERENCES......Page 399 Nanosystems......Page 403 Dendrimers......Page 404 Nanoplexes......Page 406 Liposomes......Page 407 MANUFACTURING METHODS FOR NANOPARTICLES......Page 408 NANOSURGERY......Page 409 Retinal Implants......Page 410 In Vivo Diagnosis......Page 411 Ex Vivo Diagnosis......Page 412 NANOTECHNOLOGY FOR GENE DELIVERY TO THE EYE......Page 413 NANOTECHNOLOGY FOR OCULAR DRUG DELIVERY......Page 415 TOXICITY CONCERNS WITH NANOTECHNOLOGY......Page 418 CONCLUSIONS......Page 419 REFERENCES......Page 420 CHEMISTRY AND BIOLOGIC FUNCTIONS OF ASCORBIC ACID (VITAMIN C)......Page 424 VITAMIN C AND THE RETINA......Page 426 Transporters for Ascorbate......Page 427 Transporters for DHAA......Page 428 The Blood–Retinal Barrier......Page 429 Neural Retina......Page 431 DIABETES AND RETINAL VITAMIN C STATUS......Page 432 CONCLUSIONS......Page 433 REFERENCES......Page 434 INTRODUCTION......Page 438 RATES OF TURNOVER......Page 439 SYSTEM OF EQUATIONS......Page 441 CONCLUSIONS AND PREDICTIONS FROM THE MATHEMATICAL MODEL......Page 443 REFERENCES......Page 444 back-matter.pdf......Page 446 New Work Represents Recent Discoveries And Advancements In The Study Of Ocular Transporters And Their Roles In Ocular Physiology, Pathology, And Drug Delivery. Transporters Are Found On The Membranes Of Cells And Play A Key Role In Transmitting Signals Between Cells. In This Text A Panel Of Distinguished Authors Discusse All The Latest Developments In The Study Of Ocular Transporters. Focusing On The Molecular Characteristics, Localization, And Substrate Specificities In Various Compartments Of The Eye, This Volume Discusses How Transporters Regulate The Clarity Of The Cornea And Lens, The Movements Of Fluids Across The Ciliary Epithelium, And The Transport Of Nutrients Across The Retinal Pigment Epithelium. It Also Provides An In-depth Look At How Mutations Or Dysfunction Of Specific Transporters Can Contribute To Various Disorders In The Eye, Including Blindness, And Provides Readers With Potential Targets And Strategies To Allow Safe Passage Of Therapeutic Drugs Into The E. 1 Aquaporins And Water Transport In The Cornea / Alan S. Verkman -- 2 Roles Of Corneal Epithelial Ion Transport Mechanisms In Mediating Responses To Cytokines And Osmotic Stress / Peter S. Reinach, José E. Capó-aponte, Stefan Mergler, And Kathryn S. Pokorny -- 3 Vitamin C Transport, Delivery, And Function In The Anterior Segment Of The Eye / Ram Kannan And Hovhannes J. Gukasyan -- 4 Mechanisms Of Aqueous Humor Formation: Cellular Model Of Aqueous Flow / Chi-wai Do, Chi-wing Kong, Chu-yan Chang, Mortimer M. Civan, And Chi-ho To -- 5 Membrane Transporters: New Roles In Lens Cataract / Paul J. Donaldson And Julie Lim -- 6 Lens Na+, K+-atpase / Nicholas A. Delamere And Shigeo Tamiya -- 7 Pathophysiology Of Pericyte-containing Retinal Microvessels: Roles Of Ion Channels And Transporters / Donald G. Puro -- 8 Molecular Mechanisms Of The Inner Blood-retinal Barrier Transporters / Masatoshi Tomi And Ken-ichi Hosoya -- 9 Regulation And Transport In The Rpe / Adnan Dibas And Thomas Yorio -- 10 Glucose Transporters In The Retinal Pigment Epithelium / Lawrence J. Rizzolo -- 11 Ca2+ Channels In The Retinal Pigment Epithelium: Modulators Of Retinal Pigment Epithelium Function And Communication With Neighboring Tissues / Olaf Strauss -- 12 Taurine Transport Pathways In The Outer Retina In Relation To Aging And Disease / Ali A. Hussain And John Marshall -- 13 P-glycoprotein Expression And Function In The Retinal Pigment Epithelium / Paul A. Constable, John G. Lawrenson, And N. Joan Abbott -- 14 The Retinal Rod Nckx1 And Cone/ganglion Cell Nckx2 Na+/ca2+-k+ Exchangers / Paul P.m Schnetkamp Et Al -- 15 Excitatory Amino Acid Transporters In The Retina / Vijay Sarthy And David Pow -- 16 Localization And Function Of Gamma Aminobutyric Acid Transporter 1 In The Retina / Giovanni Casini -- 17 Biochemical Defects Associated With Genetic Mutations In The Retina-specific Abc Transporter, Abcr, And Macular Degenerative Diseases / Esther E. Biswas-fiss -- 18 Glutamate Transporters And Retinal Disease And Regulation / Nigel L. Barnett And Natalie D. Bull -- 19 Glutamate Transport In Retinal Glial Cells During Diabetes / Erica L. Fletcher And Michelle M. Ward -- 20 The Emerging Significance Of Drug Transporters And Metabolizing Enzymes To Ophthalmic Drug Design / Mayssa Attar And Jie Shen -- 21 Barriers In Ocular Drug Delivery / Sriram Gunda, Sudharshan Hariharan, Nanda Mandava, And Ashim K. Mitra -- 22 Ophthalmic Applications Of Nanotechnology / Swita Raghava, Gaurav Goel, And Uday B. Kompella -- 23 Vitamin C Transporters In The Retina / Vadivel Ganapathy, Sudha Ananth, Sylvia B. Smith, And Pamela M. Martin -- 24 The Plasma Membrane Transporters And Channels Of Corneal Endothelium / Jorge Fischbarg. Edited By Joyce Tombran-tink, Colin J. Barnstable. Includes Bibliographical References And Index. Detection and responses to light are common features found throughout the plant and animal kingdoms. In most primitive life forms, a patch of light-sensitive cells make up a region containing a cell sheet devoid of any specialized anatomical structure. With the development of the eyes in more advanced life forms, light-sensing structures became more complex but primitive eyes are still in contiguity with other body tissues and fluids. The evolution of the eyeball promoted an increase in visual acuity and visual processing that, in turn, allowed vision to become the dominant sensory system for many species, including humans. The formation of a totally enclosed structure, however, required a unique set of solutions to enable the eye to control its environment. Like most organs, the eye evolved a series of homeostatic mechanisms to regulate its environment within tightly controlled limits. Unlike most organs, however, this advanced light-sensing structure has a series of requirements that place a tremendous burden on molecules that are responsible for controlling ocular homeostasis. There are many sig naling molecules and pathways that work in parallel or through crosstalk to maintain the normal ocular environment required for visual function. Perhaps none are so critical as the group of membrane molecules that are collectively termed transporters. These molecules are responsible for the controlled and selective movements of ions, nutrients, and fluid across various ocular layers necessary to optimize the internal milieu to p- serve visual function.