Investigative Ophthalmology & Visual Science, Vol 35, 2693-2699, Copyright © 1994 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats

MO Tso, C Zhang, AS Abler, CJ Chang, F Wong, GQ Chang and TT Lam
Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of Illinois at Chicago College of Medicine 60612.

PURPOSE. To determine the pathogenetic mechanism of photoreceptor cell degeneration in the inherited retinal dystrophy in Royal College of Surgeons (RCS) rats. METHODS. The dystrophic retinas of the pink-eyed RCS (RCS-rdy-p) rats were examined for DNA fragmentation by agarose gel electrophoresis of retinal DNA and by TdT-mediated biotin-dUDP nick-end labeling (TUNEL) in paraffin sections. Rats ranging in age from 3 to 60 days were examined. RESULTS. Agarose gel electrophoresis of retinal DNA isolated from animals 25, 30, 35, and 40 days old showed a ladder pattern of degradation with bands corresponding to multiples of 180 to 200 base pair subunits. TUNEL study showed increasing labeling of photoreceptor cells with progression of the retinal dystrophy of the RCS rats. CONCLUSIONS. Apoptosis is the dominant mechanism of photoreceptor degeneration in the RCS rat, which has a genetic defect in the phagocytic activity of retinal pigment epithelium. The onset of the degeneration appeared to vary between rod cells in the different regions of the eye.

This article has been cited by other articles:

				P Charbel Issa, H J Bolz, I Ebermann, E Domeier, F G Holz, and H P N Scholl Characterisation of severe rod-cone dystrophy in a consanguineous family with a splice site mutation in the MERTK gene Br J Ophthalmol, July 1, 2009; 93(7): 920 - 925. [Abstract] [Full Text] [PDF]

				B. A. Berkowitz, M. Gradianu, S. Schafer, Y. Jin, A. Porchia, R. Iezzi, and R. Roberts Ionic Dysregulatory Phenotyping of Pathologic Retinal Thinning with Manganese-Enhanced MRI Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3178 - 3184. [Abstract] [Full Text] [PDF]

				Y. Kanan, G. Moiseyev, N. Agarwal, J.-X. Ma, and M. R. Al-Ubaidi Light Induces Programmed Cell Death by Activating Multiple Independent Proteases in a Cone Photoreceptor Cell Line Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 40 - 51. [Abstract] [Full Text] [PDF]

				H. Tomita, Y. Kotake, and R. E. Anderson Mechanism of Protection from Light-Induced Retinal Degeneration by the Synthetic Antioxidant Phenyl-N-tert-Butylnitrone Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 427 - 434. [Abstract] [Full Text] [PDF]

				S. Machida, M. Tanaka, T. Ishii, K. Ohtaka, T. Takahashi, and Y. Tazawa Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 4174 - 4182. [Abstract] [Full Text] [PDF]

				H. P. N. Scholl, N. H. V. Chong, A. G. Robson, G. E. Holder, A. T. Moore, and A. C. Bird Fundus Autofluorescence in Patients with Leber Congenital Amaurosis Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2747 - 2752. [Abstract] [Full Text] [PDF]

				I. El Ghrably, D. G. Powe, G. Orr, D. Fischer, R. McIntosh, H. S. Dua, and P. J. Tighe Apoptosis in Proliferative Vitreoretinopathy Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1473 - 1479. [Abstract] [Full Text] [PDF]

				C. Jomary, R. M. Darrow, P. Wong, D. T. Organisciak, and S. E. Jones Expression of Neurturin, Glial Cell Line-Derived Neurotrophic Factor, and Their Receptor Components in Light-Induced Retinal Degeneration Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1240 - 1246. [Abstract] [Full Text] [PDF]

				F. Li, W. Cao, and R. E. Anderson Alleviation of Constant-Light-Induced Photoreceptor Degeneration by Adaptation of Adult Albino Rat to Bright Cyclic Light Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4968 - 4975. [Abstract] [Full Text] [PDF]

				I. Ranchon, M. M. LaVail, Y. Kotake, and R. E. Anderson Free Radical Trap Phenyl-N-tert-Butylnitrone Protects against Light Damage But Does Not Rescue P23H and S334ter Rhodopsin Transgenic Rats from Inherited Retinal Degeneration J. Neurosci., July 9, 2003; 23(14): 6050 - 6057. [Abstract] [Full Text] [PDF]

				N. P. Rotstein, L. E. Politi, O. L. German, and R. Girotti Protective Effect of Docosahexaenoic Acid on Oxidative Stress-Induced Apoptosis of Retina Photoreceptors Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2252 - 2259. [Abstract] [Full Text] [PDF]

				J. L. Duncan, M. M. LaVail, D. Yasumura, M. T. Matthes, H. Yang, N. Trautmann, A. V. Chappelow, W. Feng, H. S. Earp, G. K. Matsushima, et al. An RCS-Like Retinal Dystrophy Phenotype in Mer Knockout Mice Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 826 - 838. [Abstract] [Full Text] [PDF]

				W.-C. Wu, C.-C. Lai, S.-L. Chen, X. Xiao, T.-L. Chen, R. J.-F. Tsai, S.-W. Kuo, and Y.-P. Tsao Gene Therapy for Detached Retina by Adeno-Associated Virus Vector Expressing Glial Cell Line-Derived Neurotrophic Factor Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3480 - 3488. [Abstract] [Full Text] [PDF]

				M. G. Yefimova, J.-C. Jeanny, N. Keller, C. Sergeant, X. Guillonneau, C. Beaumont, and Y. Courtois Impaired Retinal Iron Homeostasis Associated with Defective Phagocytosis in Royal College of Surgeons Rats Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 537 - 545. [Abstract] [Full Text] [PDF]

				D. Vollrath, W. Feng, J. L. Duncan, D. Yasumura, P. M. D'Cruz, A. Chappelow, M. T. Matthes, M. A. Kay, and M. M. LaVail Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk PNAS, October 5, 2001; (2001) 221364198. [Abstract] [Full Text] [PDF]

				S. Machida, P. Chaudhry, T. Shinohara, D. P. Singh, V. N. Reddy, L. T. Chylack Jr, P. A. Sieving, and R. A. Bush Lens Epithelium-Derived Growth Factor Promotes Photoreceptor Survival in Light-Damaged and RCS Rats Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 1087 - 1095. [Abstract] [Full Text]

				I. Nir, J. M. Harrison, C. Liu, and R. Wen Extended Photoreceptor Viability by Light Stress in the RCS Rats but not in the Opsin P23H Mutant Rats Invest. Ophthalmol. Vis. Sci., March 1, 2001; 42(3): 842 - 849. [Abstract] [Full Text]

				D. Lau, L. H. McGee, S. Zhou, K. G. Rendahl, W. C. Manning, J. A. Escobedo, and J. G. Flannery Retinal Degeneration Is Slowed in Transgenic Rats by AAV-Mediated Delivery of FGF-2 Invest. Ophthalmol. Vis. Sci., October 1, 2000; 41(11): 3622 - 3633. [Abstract] [Full Text]

				Y. Wang, B. Detrick, Z.-X. Yu, J. Zhang, L. Chesky, and J. J. Hooks The Role of Apoptosis within the Retina of Coronavirus-Infected Mice Invest. Ophthalmol. Vis. Sci., September 1, 2000; 41(10): 3011 - 3018. [Abstract] [Full Text]

				H.-K. Poon, M. O. M. Tso, and T. T. Lam c-Fos Protein in Photoreceptor Cell Death after Photic Injury in Rats Invest. Ophthalmol. Vis. Sci., August 1, 2000; 41(9): 2755 - 2758. [Abstract] [Full Text]

				E. S. Green, M. D. Menz, M. M. LaVail, and J. G. Flannery Characterization of Rhodopsin Mis-sorting and Constitutive Activation in a Transgenic Rat Model of Retinitis Pigmentosa Invest. Ophthalmol. Vis. Sci., May 1, 2000; 41(6): 1546 - 1553. [Abstract] [Full Text]

				I. Nir, W. Kedzierski, J. Chen, and G. H. Travis Expression of Bcl-2 Protects against Photoreceptor Degeneration in retinal degeneration slow (rds) Mice J. Neurosci., March 15, 2000; 20(6): 2150 - 2154. [Abstract] [Full Text] [PDF]

				N. Katai, T. Kikuchi, H. Shibuki, S. Kuroiwa, J. Arai, T. Kurokawa, and N. Yoshimura Caspaselike Proteases Activated in Apoptotic Photoreceptors of Royal College of Surgeons Rats Invest. Ophthalmol. Vis. Sci., July 1, 1999; 40(8): 1802 - 1886. [Abstract] [Full Text] [PDF]

				Y. Uteza, J.-S. Rouillot, A. Kobetz, D. Marchant, S. Pecqueur, E. Arnaud, H. Prats, J. Honiger, J.-L. Dufier, M. Abitbol, et al. Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats PNAS, March 16, 1999; 96(6): 3126 - 3131. [Abstract] [Full Text] [PDF]

				R. R. Krishnamoorthy, M. J. Crawford, M. M. Chaturvedi, S. K. Jain, B. B. Aggarwal, M. R. Al-Ubaidi, and N. Agarwal Photo-oxidative Stress Down-modulates the Activity of Nuclear Factor-kappa B via Involvement of Caspase-1, Leading to Apoptosis of Photoreceptor Cells J. Biol. Chem., February 5, 1999; 274(6): 3734 - 3743. [Abstract] [Full Text] [PDF]

				C Jomary, G Chatelain, D Michel, A Weston, M. Neal, and S. Jones Effect of targeted expression of clusterin in photoreceptor cells on retinal development and differentiation J. Cell Sci., January 5, 1999; 112(10): 1455 - 1464. [Abstract] [PDF]

				D. R. Hinton, S. He, and P. F. Lopez Apoptosis in Surgically Excised Choroidal Neovascular Membranes in Age-Related Macular Degeneration Arch Ophthalmol, February 1, 1998; 116(2): 203 - 209. [Abstract] [Full Text] [PDF]

				R. Adler Mechanisms of Photoreceptor Death in Retinal Degenerations: From the Cell Biology of the 1990s to the Ophthalmology of the 21st Century? Arch Ophthalmol, January 1, 1996; 114(1): 79 - 83. [Abstract] [PDF]

				F. Wong Photoreceptor Apoptosis in Animal Models: Implications for Retinitis Pigmentosa Research Arch Ophthalmol, October 1, 1995; 113(10): 1245 - 1247. [Abstract] [PDF]

				C.-J. Chang, W. W. Lai, D. P. Edward, and M. O. M. Tso Apoptotic Photoreceptor Cell Death After Traumatic Retinal Detachment in Humans Arch Ophthalmol, July 1, 1995; 113(7): 880 - 886. [Abstract] [PDF]

				D. Vollrath, W. Feng, J. L. Duncan, D. Yasumura, P. M. D'Cruz, A. Chappelow, M. T. Matthes, M. A. Kay, and M. M. LaVail Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk PNAS, October 23, 2001; 98(22): 12584 - 12589. [Abstract] [Full Text] [PDF]