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6. Diabetes-Induced Impairment in Visual Function in Mice: Contributions of p38 MAPK, RAGE, Leukocytes, and Aldose ReductaseVisual Function in Diabetic Mice

Author

Lee, Chieh Allen, Li, Guangyuan, Patel, Mansi D, Petrash, J Mark, Benetz, Beth Ann, Veenstra, Alex, Amengual, Jaume, von Lintig, Johannes, Burant, Christopher J, Tang, Johnny, and Kern, Timothy S

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Diabetes, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Eye, Aldehyde Reductase, Analysis of Variance, Animals, Contrast Sensitivity, Diabetes Mellitus, Experimental, Diabetic Retinopathy, Disease Models, Animal, Leukocytes, Mice, Mice, Inbred C57BL, Psychophysics, Receptor for Advanced Glycation End Products, Receptors, Immunologic, Sensory Thresholds, Space Perception, p38 Mitogen-Activated Protein Kinases, contrast senstivity, diabetic retinopathy, spatial frequency threshold, Biological Sciences, Medical and Health Sciences, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeVisual function is impaired in diabetes, but molecular causes of this dysfunction are not clear. We assessed effects of diabetes on visual psychophysics in mice, and tested the effect of therapeutic approaches reported previously to inhibit vascular lesions of the retinopathy.MethodsWe used the optokinetic test to assess contrast sensitivity and spatial frequency threshold in diabetic C57Bl/6J mice and age-matched nondiabetic controls between 2 and 10 months of diabetes. Contributions of p38 MAP kinase (MAPK), receptor for advanced glycation end products (RAGE), leukocytes, and aldose reductase (AR) to the defect in contrast sensitivity were investigated. Cataract, a potential contributor to reductions in vision, was scored.ResultsDiabetes of 2 months' duration impaired contrast sensitivity and spatial frequency threshold in mice. The defect in contrast sensitivity persisted for at least 10 months, and cataract did not account for this impairment. Diabetic mice deficient in AR were protected significantly from development of the diabetes-induced defects in contrast sensitivity and spatial frequency threshold. In contrast, pharmacologic inhibition of p38 MAPK or RAGE, or deletion of inducible nitrous oxide synthase (iNOS) from bone marrow-derived cells did not protect the visual function in diabetes.ConclusionsDiabetes reduces spatial frequency threshold and contrast sensitivity in mice, and the mechanism leading to development of these defects involves AR. The mechanism by which AR contributes to the diabetes-induced defect in visual function can be probed by identifying which molecular abnormalities are corrected by AR deletion, but not other therapies that do not correct the defect in visual function.

Published
2014

8. Donor Age and Factors Related to Endothelial Cell Loss 10 Years after Penetrating Keratoplasty Specular Microscopy Ancillary Study

Author

Group, Writing Committee for the Cornea Donor Study Research, Lass, Jonathan H, Benetz, Beth Ann, Gal, Robin L, Kollman, Craig, Raghinaru, Dan, Dontchev, Mariya, Mannis, Mark J, Holland, Edward J, Chow, Christopher, McCoy, Kristen, Price, Francis W, Sugar, Alan, Verdier, David D, and Beck, Roy W

Subjects
Transplantation, Clinical Trials and Supportive Activities, Eye Disease and Disorders of Vision, Clinical Research, Eye, Adolescent, Adult, Aged, Aging, Cell Count, Child, Corneal Edema, Corneal Endothelial Cell Loss, Double-Blind Method, Endothelium, Corneal, Eye Banks, Female, Fuchs' Endothelial Dystrophy, Graft Survival, Humans, Keratoplasty, Penetrating, Male, Middle Aged, Postoperative Complications, Prospective Studies, Risk Factors, Time Factors, Tissue Donors, Young Adult, Writing Committee for the Cornea Donor Study Research Group, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

ObjectiveTo examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP).DesignMulticenter, prospective, double-masked clinical trial.ParticipantsWe included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema).MethodsCorneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD).Main outcome measuresEndothelial cell density at 10 years.ResultsAmong study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P1000 cells/mm(2).ConclusionsSubstantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.

Published
2013

9. The Effect of Donor Age on Penetrating Keratoplasty for Endothelial Disease Graft Survival after 10 Years in the Cornea Donor Study

Author

Group, Writing Committee for the Cornea Donor Study Research, Mannis, Mark J, Holland, Edward J, Gal, Robin L, Dontchev, Mariya, Kollman, Craig, Raghinaru, Dan, Dunn, Steven P, Schultze, Robert L, Verdier, David D, Lass, Jonathan H, Raber, Irving M, Sugar, Joel, Gorovoy, Mark S, Sugar, Alan, Stulting, R Doyle, Montoya, Monty M, Penta, Jeffrey G, Benetz, Beth Ann, and Beck, Roy W

Subjects
Eye Disease and Disorders of Vision, Clinical Trials and Supportive Activities, Transplantation, Clinical Research, Eye, Adolescent, Adult, Age Factors, Aged, Aging, Child, Corneal Edema, Double-Blind Method, Eye Banks, Female, Follow-Up Studies, Fuchs' Endothelial Dystrophy, Graft Survival, Humans, Keratoplasty, Penetrating, Male, Middle Aged, Prospective Studies, Registries, Tissue Donors, Young Adult, Writing Committee for the Cornea Donor Study Research Group, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

ObjectiveTo determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age.DesignMulticenter, prospective, double-masked clinical trial.ParticipantsA total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years.MethodsForty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines.Main outcome measuresGraft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months.ResultsIn the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P

Published
2013

12. Prelamellar Dissection Donor Corneal Thickness Is Associated With Descemet Stripping Automated Endothelial Keratoplasty Operative Complications in the Cornea Preservation Time Study

Author

Ross, Kevin W., Stoeger, Christopher G., Rosenwasser, George O. D., OʼBrien, Robert C., Szczotka-Flynn, Loretta B., Ayala, Allison R., Maguire, Maureen G., Benetz, Beth Ann, Dahl, Patricia, Drury, Donna C., Dunn, Steven P., Farazdaghi, Sameera M., Hoover, Caroline K., Macsai, Marian S., Mian, Shahzad I., Nordlund, Michael L., Penta, Jeffrey G., Soper, Mark C., Terry, Mark A., Verdier, David D., Williams, Doyce V., and Lass, Jonathan H.

Published
2019
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20. Corneal Endothelial Cell Loss 3 Years After Successful Descemet Stripping Automated Endothelial Keratoplasty in the Cornea Preservation Time Study: A Randomized Clinical Trial

Author

Lass, Jonathan H., Benetz, Beth Ann, Verdier, David D., Szczotka-Flynn, Loretta B., Ayala, Allison R., Liang, Wendi, Aldave, Anthony J., Dunn, Steven P., McCall, Tyrone, Mian, Shahzad I., Navarro, Lisa C., Patel, Sanjay V., Pramanik, Sudeep, Rosenwasser, George O., Ross, Kevin W., Terry, Mark A., Kollman, Craig, Gal, Robin L., and Beck, Roy W.

Published
2017
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21. Descemet Endothelial Thickness Comparison Trial: Two-Year Results from a Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty

Author

Rose-Nussbaumer, Jennifer, primary, Lin, Charles C., additional, Austin, Ariana, additional, Liu, Zijun, additional, Clover, Jameson, additional, McLeod, Stephen D., additional, Porco, Travis C., additional, Lietman, Thomas M., additional, Dresner, Samuel M., additional, Benetz, Beth Ann, additional, Lass, Jonathan H., additional, and Chamberlain, Winston D., additional

Published
2021
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25. Specular Microscopy

Author

Benetz, Beth Ann, primary, Yee, Richard, additional, Bidros, Maria, additional, and Lass, Jonathan, additional

Published
2011
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26. Contributors

Author

Abbott, Richard L, primary, Adrean, Sean D, additional, Al-Muammar, Abdulrahman, additional, Akhtar, Jihan, additional, Alfonso, Eduardo C, additional, Allen, Richard C, additional, Almond, M Camille, additional, Alvarenga, Lênio, additional, Alward, Wallace LM, additional, Ambrósio, Renato, additional, Anwar, Mohammad, additional, Azar, Dimitri T, additional, Ball, James L, additional, Barney, Neal P, additional, Bartow, Rebecca M, additional, Baum, Jules, additional, Belin, Michael W, additional, Bell, Jason H, additional, Benetz, Beth Ann, additional, Berbos, Zachary, additional, Beuerman, Roger W, additional, Bhasin, Arpita Kadakia, additional, Bhat, Pooja V, additional, Biber, Joseph M, additional, Bidros, Maria, additional, Birnbaum, Andrea D, additional, Bouchard, Charles S, additional, Bradley, Jay C, additional, Brandt, James D, additional, Brasington, Richard D, additional, Brilakis, Harilaos S, additional, Burkat, Cat N, additional, Calatayud, Marta, additional, Cameron, J Douglas, additional, Campos, Mauro, additional, Carpel, Emmett F, additional, Cavanagh, H Dwight, additional, Chan, Cordelia, additional, Chang, Richard I, additional, Chang, Bernard H, additional, Chern, Kenneth C, additional, Ching, Steven, additional, Chodosh, James, additional, Choo, Phillip H, additional, Chung, Gary, additional, Ciolino, Joseph B, additional, Clayton, Janine A, additional, Cohen, Elisabeth J, additional, Comyn, Oliver, additional, Cortina, M Soledad, additional, Cowden, John W, additional, Croasdale, Christopher R, additional, Davidson, Richard S, additional, Davis, Elizabeth A, additional, Daya, Sheraz M, additional, Freitas, Denise de, additional, DeMill, David L, additional, de Oliveira, Lauro Augusto, additional, de Smet, Marc D, additional, de Sousa, Luciene B, additional, Djalilian, Ali R, additional, Dohlman, Claes H, additional, Donnenfeld, Eric D, additional, Dortzbach, Richard K, additional, Driebe, William T, additional, Dunn, Steven P, additional, Eagle, Ralph C, additional, Edelstein, Sean L, additional, Eiferman, Richard A, additional, Eliason, Joseph A, additional, Farid, Marjan, additional, Faulkner, William J, additional, Feder, Robert S, additional, Feiz, Vahid, additional, Feng, Matthew T, additional, Fingert, John H, additional, Florakis, George J, additional, Fontana, Luigi, additional, Forster, Richard K, additional, Foster, C Stephen, additional, Foster, F Stuart, additional, Foulks, Gary N, additional, Friedlander, Mitchell H, additional, Fukuda, Masahiko, additional, Galor, Anat, additional, Gan, Theresa J, additional, Garg, Prashant, additional, Garg, Sumit, additional, Glasser, David B, additional, Goins, Kenneth M, additional, Goldstein, Debra A, additional, Gottlieb, Chloe, additional, Grimmett, Michael R, additional, Gris, Oscar, additional, Groos, Erich B, additional, Gruzensky, William D, additional, Güell, Jose L, additional, Gupta, Preeya K, additional, Hamill, M Bowes, additional, Hammersmith, Kristin M, additional, Hamrah, Pedram, additional, Hannush, Sadeer B, additional, Hardten, David R, additional, Harrison, Andrew, additional, Heck, Ellen L, additional, Heidemann, David G, additional, Herman, David C, additional, Heur, J Martin, additional, Hodge, William G, additional, Hoffman, Carol J, additional, Holland, Edward J, additional, Holland, Gary N, additional, Honig, Marc A, additional, Hood, Christopher T, additional, Hoskins, Eliza N, additional, Huang, Andrew J W, additional, Huang, David, additional, Hui, Jennifer I, additional, Iuorno, Joseph D, additional, Jackson, W Bruce, additional, Jakobiec, Frederick A, additional, Jeng, Bennie H, additional, Jester, James V, additional, Jordan, David R, additional, Kaiura, Terry L, additional, Karp, Carol L, additional, Katz, Douglas G, additional, Kaufman, Stephen C, additional, Kersten, Robert C, additional, Khachikian, Stephen S, additional, Kim, Jennifer H, additional, Kim, Joung Y, additional, Kim, Stella K, additional, Kim, Terry, additional, Kirkness, Colin M, additional, Klyce, Stephen D, additional, Koch, Douglas D, additional, Kowalski, Regis P, additional, Krachmer, Jay H, additional, Laibson, Peter R, additional, Lane, Stephen S, additional, Lass, Jonathan H, additional, Lee, W Barry, additional, Lee, Olivia A, additional, Lemp, Michael A, additional, Lenhart, Phoebe D, additional, Li, Yan, additional, Liesegang, Thomas J, additional, Lim, Michele C, additional, Lin, Lily Koo, additional, Lin, Michael P, additional, Lindquist, Thomas D, additional, Lindstrom, Richard L, additional, Litoff, David, additional, Liu, Christopher, additional, Lowder, Careen Y, additional, Lubniewski, Anthony J, additional, McGee, Hall T, additional, McLean, Ian W, additional, Macsai, Marian S, additional, Manero, Felicidad, additional, Mannis, Mark J, additional, Mantopoulos, Dimosthenis, additional, Martinez, Carlos E, additional, Mártonyi, Csaba L, additional, Mashor, Raneen S, additional, Mathers, William D, additional, Mehta, Manisha N, additional, Meisler, David M, additional, Mian, Shahzad I, additional, Miller, Darlene, additional, Miller, Corey A, additional, Montoya, Monty, additional, Morral, Merce, additional, Moyes, Andrew L, additional, Murphy, Michael L, additional, Nassiri, Nariman, additional, Neff, Kristiana D, additional, Nelson, J Daniel, additional, Nerad, Jeffrey A, additional, Netto, Marcelo V, additional, Newton, Christopher J, additional, Nijm, Lisa M, additional, Nishida, Teruo, additional, Noble, Bruce A, additional, Nordlund, Michael L, additional, Nussenblatt, Robert B, additional, O'Day, David G, additional, Ongkosuwito, Jenny V, additional, Oxford, Karen W, additional, Palay, David A, additional, Palmon, Florentino E, additional, Paranjpe, Deval R, additional, Parikh, Mansi, additional, Park, David H, additional, Park, D J John, additional, Parsons, Matthew R, additional, Pavlin, Charles J, additional, Pearlstein, Eric S, additional, Perry, Alicia, additional, Petroll, W Matthew, additional, Pfister, Daryl R, additional, Pfister, Roswell R, additional, Pflugfelder, Stephen C, additional, Price, Francis W, additional, Price, Marianne O, additional, Probst, Louis E, additional, Purcell, John J, additional, Pyott, Andrew A E, additional, Raizman, Michael B, additional, Raju, Leela V, additional, Randleman, J Bradley, additional, Rao, Gullapalli N, additional, Rapuano, Christopher J, additional, Reilly, Charles D, additional, de Candelaria Renesto, Adimara, additional, Rezende, Renata A, additional, Robertson, Danielle M, additional, Rootman, David S, additional, Rothman, Jason S, additional, Rubinfeld, Roy Scott, additional, Sadowsky, Alan E, additional, Saika, Shizuya, additional, Sakhalkar, Monali V, additional, Salz, James J, additional, Sangwan, Virender S, additional, Scarpi, Marinho, additional, Scharf, Bradley H, additional, Schmidt, Greg, additional, Schmitt, Artur, additional, Schmitt, Fernanda Piccoli, additional, Schteingart, Miriam T, additional, Schwab, Ivan R, additional, Schwam, Brian L, additional, Schwartz, Gary S, additional, Sen, H Nida, additional, Shapiro, Michael B, additional, Shimmura, Shigeto, additional, Singal, Neera, additional, Skeens, Heather M, additional, Skolnick, Craig A, additional, Slomovic, Allan R, additional, Smith, Janine A, additional, Snyder, Michael E, additional, Solomon, Renée, additional, Soukiasian, Sarkis H, additional, Srinivasan, Sathish, additional, Stamler, John F, additional, Steinert, Roger F, additional, Stoller, Glenn L, additional, Streeten, Barbara W, additional, Stulting, R Doyle, additional, Sugar, Alan, additional, Sugar, Joel, additional, Tan, Donald, additional, Tauber, Joseph, additional, Terry, Mark A, additional, Tessler, Howard H, additional, Torrabadella, Marta, additional, Traboulsi, Elias I, additional, Trattler, William B, additional, Tsai, Julie H, additional, Tse, David T, additional, Tu, Elmer Y, additional, Ursea, Roxana, additional, Vaddavalli, Pravin K, additional, Van Meter, Woodford S, additional, Varley, Gary A, additional, Vasaiwala, Roshni, additional, Verachtert, Anthony J, additional, Verdier, David D, additional, Vieira, Ana Carolina, additional, Virasch, Vanee V, additional, Wang, Li, additional, Waring, George O, additional, Warner, Michael A, additional, Warrian, Kevin J, additional, Webster, Guy F, additional, Weikert, Mitchell P, additional, Weisenthal, Robert W, additional, Weiss, Jayne S, additional, Wichiensin, Pongmas, additional, Wilhelmus, Kirk R, additional, Wilson, Steven E, additional, Woodward, Maria A, additional, Yee, Richard W, additional, and Yoo, Sonya, additional

Published
2011
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28. Comparative corneal endothelial cell toxicity of differing intracameral moxifloxacin doses after phacoemulsification

Author

Chang, David F., primary, Prajna, N. Venkatesh, additional, Szczotka-Flynn, Loretta B., additional, Benetz, Beth Ann, additional, Lass, Jonathan H., additional, O'Brien, Robert C., additional, Menegay, Harry J., additional, Gardner, Susanne, additional, Shekar, Madhu, additional, Rajendrababu, Sharmila, additional, and Rhee, Douglas J., additional

Published
2020
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32. Postoperative Endothelial Cell Density Is Associated with Late Endothelial Graft Failure after Descemet Stripping Automated Endothelial Keratoplasty

Author

Patel, Sanjay V., primary, Lass, Jonathan H., additional, Benetz, Beth Ann, additional, Szczotka-Flynn, Loretta B., additional, Cohen, Nathan J., additional, Ayala, Allison R., additional, Maguire, Maureen G., additional, Drury, Donna C., additional, Dunn, Steven P., additional, Jeng, Bennie H., additional, Jones, Marc F., additional, Menegay, Harry J., additional, Oliva, Matthew S., additional, Rosenwasser, George O.D., additional, Seedor, John A., additional, Terry, Mark A., additional, and Verdier, David D., additional

Published
2019
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33. Effect of Graft Attachment Status and Intraocular Pressure on Descemet Stripping Automated Endothelial Keratoplasty Outcomes in the Cornea Preservation Time Study

Author

Aldave, Anthony J., primary, Terry, Mark A., additional, Szczotka-Flynn, Loretta B., additional, Liang, Wendi, additional, Ayala, Allison R., additional, Maguire, Maureen G., additional, O'Brien, Robert C., additional, Benetz, Beth Ann, additional, Bokosky, John E., additional, Dunn, Steven P., additional, Gillette, Thomas E., additional, Hammersmith, Kristin M., additional, Hardten, David R., additional, Jeng, Bennie H., additional, Jones, Marc F., additional, Lindstrom, Richard L., additional, Maverick, Kenneth J., additional, Nirankari, Verinder S., additional, Oliva, Matthew S., additional, Raber, Irving M., additional, Rapuano, Christopher J., additional, Rosenwasser, George O.D., additional, Ross, Kevin W., additional, Seedor, John W., additional, Shamie, Neda, additional, Stoeger, Christopher G., additional, Tauber, Shachar, additional, Van Meter, Woodford S., additional, Verdier, David D., additional, and Lass, Jonathan H., additional

Published
2019
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34. Factors Associated With Graft Rejection in the Cornea Preservation Time Study

Author

Stulting, R. Doyle, primary, Lass, Jonathan H., additional, Terry, Mark A., additional, Benetz, Beth Ann, additional, Cohen, Nathan J., additional, Ayala, Allison R., additional, Maguire, Maureen G., additional, Croasdale, Christopher, additional, Daoud, Yassine J., additional, Dunn, Steven P., additional, Goins, Kenneth M., additional, Gupta, Pankaj C., additional, Macsai, Marian S., additional, Mian, Shahzad I., additional, Pramanik, Sudeep, additional, Rose-Nussbaumer, Jennifer, additional, Song, Jonathan C., additional, Stark, Walter J., additional, Sugar, Alan, additional, Verdier, David D., additional, and Szczotka-Flynn, Loretta B., additional

Published
2018
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38. Effects of Repeated Intravitreal Aflibercept Injection on the Corneal Endothelium in Patients With Age-Related Macular Degeneration: Outcomes From the RE-VIEW Study

Author

Lass, Jonathan H., primary, Benetz, Beth Ann, additional, Menegay, Harry J., additional, Tsipis, Constantinos P., additional, Cook, Jane Caty, additional, Boyer, David S., additional, Singer, Michael, additional, Erickson, Kristine, additional, Saroj, Namrata, additional, Vitti, Robert, additional, Chu, Karen W., additional, Moini, Hadi, additional, Soo, Yuhwen, additional, and Cheng, Yenchieh, additional

Published
2018
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41. Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study.

Author

Lass, Jonathan H., Benetz, Beth Ann, Patel, Sanjay V., Szczotka-Flynn, Loretta B., O'Brien, Robert, Ayala, Allison R., Maguire, Maureen G., Daoud, Yassine J., Greiner, Mark A., Hannush, Sadeer B., Lee, W. Barry, Mauger, Thomas F., Menegay, Harry J., Mifflin, Mark D., Raizman, Michael B., Rose-Nussbaumer, Jennifer, Schultze, Robert L., Schmidt, Gregory A., Sugar, Alan, and Terry, Mark A.

Published
2019
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42. Diabetes-induced impairment in visual function in mice: contributions of p38 MAPK, rage, leukocytes, and aldose reductase

Author

Lee, Chieh Allen, Li, Guangyuan, Patel, Mansi D, Petrash, J Mark, Benetz, Beth Ann, Veenstra, Alex, Amengual, Jaume, von Lintig, Johannes, Burant, Christopher J, Tang, Johnny, and Kern, Timothy S

Subjects
Receptor for Advanced Glycation End Products, Inbred C57BL, Eye, Ophthalmology & Optometry, p38 Mitogen-Activated Protein Kinases, Autoimmune Disease, Medical and Health Sciences, Contrast Sensitivity, Mice, Experimental, Aldehyde Reductase, Immunologic, Receptors, Leukocytes, Diabetes Mellitus, Psychophysics, Animals, 2.1 Biological and endogenous factors, Aetiology, Eye Disease and Disorders of Vision, contrast senstivity, Metabolic and endocrine, Analysis of Variance, Diabetic Retinopathy, Animal, Diabetes, Biological Sciences, diabetic retinopathy, Sensory Thresholds, Space Perception, Disease Models, spatial frequency threshold
Abstract

PurposeVisual function is impaired in diabetes, but molecular causes of this dysfunction are not clear. We assessed effects of diabetes on visual psychophysics in mice, and tested the effect of therapeutic approaches reported previously to inhibit vascular lesions of the retinopathy.MethodsWe used the optokinetic test to assess contrast sensitivity and spatial frequency threshold in diabetic C57Bl/6J mice and age-matched nondiabetic controls between 2 and 10 months of diabetes. Contributions of p38 MAP kinase (MAPK), receptor for advanced glycation end products (RAGE), leukocytes, and aldose reductase (AR) to the defect in contrast sensitivity were investigated. Cataract, a potential contributor to reductions in vision, was scored.ResultsDiabetes of 2 months' duration impaired contrast sensitivity and spatial frequency threshold in mice. The defect in contrast sensitivity persisted for at least 10 months, and cataract did not account for this impairment. Diabetic mice deficient in AR were protected significantly from development of the diabetes-induced defects in contrast sensitivity and spatial frequency threshold. In contrast, pharmacologic inhibition of p38 MAPK or RAGE, or deletion of inducible nitrous oxide synthase (iNOS) from bone marrow-derived cells did not protect the visual function in diabetes.ConclusionsDiabetes reduces spatial frequency threshold and contrast sensitivity in mice, and the mechanism leading to development of these defects involves AR. The mechanism by which AR contributes to the diabetes-induced defect in visual function can be probed by identifying which molecular abnormalities are corrected by AR deletion, but not other therapies that do not correct the defect in visual function.

Published
2014

43. Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study

Author

Writing Committee for the Cornea Donor Study Research Group, Lass, Jonathan H, Benetz, Beth Ann, Gal, Robin L, Kollman, Craig, Raghinaru, Dan, Dontchev, Mariya, Mannis, Mark J, Holland, Edward J, Chow, Christopher, McCoy, Kristen, Price, Francis W, Sugar, Alan, Verdier, David D, and Beck, Roy W

Subjects
Adult, Male, Aging, Time Factors, Adolescent, Clinical Trials and Supportive Activities, Clinical Sciences, Cell Count, Eye Banks, Eye, Ophthalmology & Optometry, Writing Committee for the Cornea Donor Study Research Group, Young Adult, Postoperative Complications, Penetrating, Double-Blind Method, Risk Factors, Clinical Research, Opthalmology and Optometry, Humans, Endothelium, Prospective Studies, Child, Eye Disease and Disorders of Vision, Aged, Transplantation, Fuchs' Endothelial Dystrophy, Corneal Edema, Graft Survival, Corneal, Middle Aged, Corneal Endothelial Cell Loss, Tissue Donors, Keratoplasty, Public Health and Health Services, Female
Abstract

ObjectiveTo examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP).DesignMulticenter, prospective, double-masked clinical trial.ParticipantsWe included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema).MethodsCorneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD).Main outcome measuresEndothelial cell density at 10 years.ResultsAmong study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P1000 cells/mm(2).ConclusionsSubstantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.

Published
2013

44. The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the Cornea Donor Study

Author

Writing Committee for the Cornea Donor Study Research Group, Mannis, Mark J, Holland, Edward J, Gal, Robin L, Dontchev, Mariya, Kollman, Craig, Raghinaru, Dan, Dunn, Steven P, Schultze, Robert L, Verdier, David D, Lass, Jonathan H, Raber, Irving M, Sugar, Joel, Gorovoy, Mark S, Sugar, Alan, Stulting, R Doyle, Montoya, Monty M, Penta, Jeffrey G, Benetz, Beth Ann, and Beck, Roy W

Subjects
Adult, Male, Aging, Adolescent, Clinical Trials and Supportive Activities, Clinical Sciences, Eye Banks, Eye, Ophthalmology & Optometry, Writing Committee for the Cornea Donor Study Research Group, Young Adult, Penetrating, Double-Blind Method, Clinical Research, Opthalmology and Optometry, Humans, Registries, Prospective Studies, Child, Eye Disease and Disorders of Vision, Aged, Transplantation, Fuchs' Endothelial Dystrophy, Corneal Edema, Graft Survival, Age Factors, Middle Aged, Tissue Donors, Keratoplasty, Public Health and Health Services, Female, Follow-Up Studies
Abstract

ObjectiveTo determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age.DesignMulticenter, prospective, double-masked clinical trial.ParticipantsA total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years.MethodsForty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines.Main outcome measuresGraft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months.ResultsIn the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P

Published
2013

45. Randomized, Prospective, Single-Masked Clinical Trial of Endothelial Keratoplasty Performance With 2 Donor Cornea 4°C Storage Solutions and Associated Chambers

Author

Price, Marianne O., primary, Knight, O'Rese J., additional, Benetz, Beth Ann, additional, Debanne, Sara M., additional, Verdier, David D., additional, Rosenwasser, George O., additional, Rosenwasser, Miriam, additional, Price, Francis W., additional, and Lass, Jonathan H., additional

Published
2015
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47. List of Contributors

Author

Abbott, Richard L, Acharya, Nisha R, Aldave, Anthony J, Alfonso, Eduardo C, Allen, Richard C, Al-Mohtaseb, Zaina, Almond, M Camille, Al-Shamekh, Shomoukh, Alvarenga, Lênio Souza, Alward, Wallace LM, Ambrósio, Renato, Jr, Ang, Andrea Y, Ang, Marcus, Anwar, Mohammad, Asbell, Penny A, Azar, Dimitri T, Bahar, Irit, Baik, Annie K, Barney, Neal P, Barry, Brendan C, Barsam, Allon, Bartow, Rebecca M, Baum, Jules, Belin, Michael W, Bell, Jason H, Benetz, Beth Ann, Beuerman, Roger W, Biber, Joseph M, Birnbaum, Andrea D, Bohm, Kelley J, Bouchard, Charles S, Bradley, Jay C, Brandt, James D, Burkat, Cat N, Busin, Massimo, Buznyk, Oleksiy, Cameron, J Douglas, Campos, Mauro, Carpel, Emmett F, Cavanagh, H Dwight, Chai, Jean SM, Chamberlain, Winston, Chan, Clara C, Chang, Bernard H, Chen, Edwin S, Chen, Michael C, Chen, Neil, Chern, Kenneth C, Chodosh, James, Chong, Elaine W, Choulakian, Mazen Y, Chung, Gary, Ciolino, Joseph B, Ciralsky, Jessica, Cortina, Maria Soledad, Crawford, Alexandra Z, de la Cruz, Jose, Damani, Mausam R, Dantas, Paulo Elias C, Darvish-Zargar, Mahshad, Davidson, Richard S, Daya, Sheraz M, Djalilian, Ali R, Donnenfeld, Eric D, Dunn, Steven P, Eagle, Ralph C, Jr, Eghrari, Allen O, Eiferman, Richard A, Eliason, Joseph A, Elies, Daniel, Fagerholm, Per, Farid, Marjan, Farooq, Asim V, Faulkner, William J, Fausett, Blake V, Feder, Robert S, Feiz, Vahid, Felberg, Sergio, Feng, Matthew T, Fontana, Luigi, Foulks, Gary N, de Freitas, Denise, Galor, Anat, Garg, Prashant, Garg, Sumit, Gensheimer, William G, Ghahari, Elham, Glasser, David B, Goins, Kenneth M, Gokoffski, Kimberly K, Goldstein, Debra A, Golen, Jeffrey R, Gomes, Jose, Gonzales, John A, Gottsch, John D, Greenstein, Steven A, Gregory, Darren G, Greiner, Mark A, Griffith, May, Gris, Oscar, Groos, Erich B, Jr, Gruzensky, William D, Güell, Jose L, Guerra, Frederico P, Gupta, Preeya K, Hamill, M Bowes, Hammersmith, Kristin M, Hamrah, Pedram, Hannush, Sadeer B, Hardten, David R, Heidemann, David G, Hersh, Peter S, Hill, Darren C, Hofling-Lima, Ana Luisa, Holland, Edward J, Holland, Gary N, Holland, Stephen, Hong, Augustine R, Honig, Marc A, Hood, Christopher T, Hoskins, Eliza N, Hou, Joshua H, Hsu, Kimberly, Huang, Andrew JW, Huang, David, Hui, Jennifer I, Iovieno, Alfonso, Iuorno, Joseph D, Jackson, W Bruce, Jacobs, Deborah S, Jakobiec, Frederick A, Jeng, Bennie H, Jester, James V, Joag, Madhura G, Jordan, David R, Kanjee, Raageen, Karp, Carol L, Kaufman, Stephen C, Keenan, Jeremy D, Kersten, Robert C, Khachikian, Stephen S, Khanna, Rohit C, Khater, Timothy T, Kim, Eric J, Kim, Michelle J, Kim, Stella K, Kim, Terry, Kinoshita, Shigeru, Kirkness, Colin M, Klyce, Stephen D, Koch, Douglas D, Kohnen, Thomas, Koizumi, Noriko, Kook, Daniel, Kowalski, Regis P, Kruse, Friedrich E, Lai, Edward, Laibson, Peter R, Lass, Jonathan H, Lee, Samuel H, Lee, W Barry, Lemp, Michael A, Li, Jennifer Y, Li, Yan, Lietman, Thomas M, Lim, Michele C, Lin, Lily Koo, Lindquist, T Peter, Lindquist, Thomas D, Lindquist, Timothy P, Lindstrom, Richard L, Litoff, David, Liu, Yu-Chi, Livny, Eitan, LoVerde, Lorena, Lowder, Careen Y, Luz, Allan, Macsai, Marian S, Maio, Mark, Malling, Jackie V, Maltry, Amanda C, Mand, Paramdeep S, Manero, Felicidad, Mannis, Mark J, Mannis, Tova, Martinez, Carlos E, Mártonyi, Csaba L, de la Maza, Maite Sainz, McGee, Hall T, McGhee, Charles NJ, Mehta, Jodhbir, Meisler, David M, Van Meter, Woodford S, Meyer, Jay J, Mian, Shahzad I, Miller, Darlene, Morishige, Naoyuki, Morral, Merce, Moshirfar, Majid, Moss, Adam, Movahedan, Asadolah, Nagra, Parveen, Nanji, Afshan A, Neems, Leslie C, Neff, Kristiana D, Nelson, J Daniel, Nerad, Jeffrey A, Netto, Marcelo V, Ng, Jacqueline, Nijm, Lisa M, Nischal, Ken K, Nishida, Teruo, Nishiwaki-Dantas, M Cristina, Nuijts, Rudy MMA, Nussenblatt, Robert B, Oxford, Karen W, Palay, David A, Palioura, Sotiria, Paranjpe, Deval R, Parikh, Mansi, Parsons, Matthew R, Pasadhika, Sirichai, Patel, Dipika V, Pavlin, Charles J, Pearlstein, Eric S, Pepose, Jay S, Peralta, Robert J, Perez, Mauricio A, Perez, Victor L, Perry, Alicia, Petroll, W Matthew, Pflugfelder, Stephen C, Price, Francis W, Jr, Price, Marianne O, Probst, Louis E, Raizman, Michael B, Raju, Leela V, Rao, Gullapalli N, Raoof, Duna, Rapuano, Christopher J, Reddy, Jagadesh C, Redenbo, Ellen, Reidy, James J, Reilly, Charles D, da Candelaria Renesto, Adimara, Riau, Andri K, Riveroll-Hannush, Lorena, Rizzuti, Allison E, Robertson, Danielle M, Rohr, Ashley, Rootman, David S, Rosenbaum, James T, Sadowsky, Alan E, Saika, Shizuya, Saldanha, Mario J, Salz, James J, Sangwan, Virender S, Sarnicola, Caterina, Sarnicola, Enrica, Sarnicola, Vincenzo, Sayed-Ahmed, Ibrahim O, Sayegh, Rony R, Schmidt, Gregory A, Schteingart, Miriam T, Schwab, Ivan R, Schwam, Brian L, Schwartz, Gary S, Scorcia, Vincenzo, Sen, H Nida, Severinsky, Boris, Shah, Kevin J, Shajari, Mehdi, Shamie, Neda, Shapiro, Brett, Shehadeh-Mashor, Raneen, Shimmura, Shigeto, Shute, Thomas S, Sierra, Patricia B, Bandeira e Silva, Francisco, Sivaraman, Kavitha R, Skolnick, Craig A, Slomovic, Allan R, Snyder, Michael E, Solomon, Renée, Soukiasian, Sarkis H, Barbosa de Sousa, Luciene, Srinivasan, Sathish, Stagner, Anna M, Starr, Christopher E, Steinert, Roger F, Stoica, Bazil TL, Straiko, Michael D, Sugar, Alan, Sugar, Joel, Ta, Christopher N, Tabbara, Khalid F, Tan, Donald TH, Tang, Maolong, Tauber, Joseph, Taylor, Shabnam, Terry, Mark A, Tessler, Howard H, Tourtas, Theofilos, Traboulsi, Elias I, Trattler, William, Trese, Matthew GJ, Tse, David T, Tu, Elmer Y, Vaddavalli, Pravin K, Valenzuela, Felipe A, Varley, Gary A, Verdier, David D, Vickers, Laura A, Vieira, Ana Carolina, Vislisel, Jesse M, Vo, An, Vo, Rosalind C, Vukich, John A, Wade, Matthew, Wang, Jay C, Wang, Li, Waring, George O, III, Waring, George O, IV, Warner, Michael A, Weikert, Mitchell P, Weinstein, Jessica E, Weiss, Jayne S, Weller, Julia M, Wilhelmus, Kirk R, Williamson, Samantha, Wilson, Steven E, Yeu, Elizabeth, Yu, Charles Q, Zhu, Dagny, and Ziaei, Mohammed

Published
2017
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48. Specular Microscopy Ancillary Study Methods for Donor Endothelial Cell Density Determination of Cornea Donor Study Images

Author

Benetz, Beth Ann, Gal, Robin L., Ruedy, Katrina J., Rice, Carmella, W, Roy, Beck, Kalajian, Andrea D., and Lass, Jonathan H.

Subjects
Quality Control, medicine.medical_specialty, Pathology, genetic structures, Image quality, Cell Count, Eye Banks, Article, Cellular and Molecular Neuroscience, Ophthalmology, Cornea, Microscopy, medicine, Humans, Observer Variation, Chemistry, Endothelium, Corneal, Reproducibility of Results, Eye bank, Ancillary Study, Sensory Systems, Tissue Donors, Endothelial cell density, medicine.anatomical_structure, SPECULAR MICROSCOPY, Corneal endothelial cell density
Abstract

To describe reliable methods for determining central corneal endothelial cell density (ECD) in a multicenter eye bank study.The Specular Microscopy Reading Center utilized a dual-grading procedure and adjudication process to classify image quality and determine ECD for a subset of donor endothelial images obtained in the Specular Microscopy Ancillary Study, which is part of the Cornea Donor Study. Two certified readers classified images as analyzable (excellent, good, fair) or unanalyzable and determined the ECD using a variable frame technique. An adjudicator also evaluated the images if quality classifications by the two readers differed by one grade, if any reader found the image unanalyzable, and/or if the ECD determination between the two readers wasor= 5%.Image quality categorization by the two readers was identical for 441 (64%) of 688 donor images. The ECD differed by5% for 442 (69%) of the 645 analyzable images. The ECD determined by the adjudicator was5% different than the ECD determined by at least one reader for 193 (95%) of the 203 remaining images.The dual-grading and adjudication procedures produce reliable, reproducible assessments of image quality and ECD. The importance of two independent readings is evident in that image quality ratings differed between the two readers by one grade in 36% of all images and ECD counts differed byor=5% for 31% of analyzable images.

Published
2006

49. The Effect of Donor Age on Penetrating Keratoplasty for Endothelial Disease

Author

Mannis, Mark J., primary, Holland, Edward J., additional, Gal, Robin L., additional, Dontchev, Mariya, additional, Kollman, Craig, additional, Raghinaru, Dan, additional, Dunn, Steven P., additional, Schultze, Robert L., additional, Verdier, David D., additional, Lass, Jonathan H., additional, Raber, Irving M., additional, Sugar, Joel, additional, Gorovoy, Mark S., additional, Sugar, Alan, additional, Stulting, R. Doyle, additional, Montoya, Monty M., additional, Penta, Jeffrey G., additional, Benetz, Beth Ann, additional, and Beck, Roy W., additional

Published
2013
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50. Donor Age and Factors Related to Endothelial Cell Loss 10 Years after Penetrating Keratoplasty

Author

Lass, Jonathan H., primary, Benetz, Beth Ann, additional, Gal, Robin L., additional, Kollman, Craig, additional, Raghinaru, Dan, additional, Dontchev, Mariya, additional, Mannis, Mark J., additional, Holland, Edward J., additional, Chow, Christopher, additional, McCoy, Kristen, additional, Price, Francis W., additional, Sugar, Alan, additional, Verdier, David D., additional, and Beck, Roy W., additional

Published
2013
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