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(Investigative Ophthalmology and Visual Science. 2001;42:842-849.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Extended Photoreceptor Viability by Light Stress in the RCS Rats but not in the Opsin P23H Mutant Rats

Izhak Nir1, Joseph M. Harrison2, Changdong Liu3 and Rong Wen3

1 From the Departments of Pharmacology and 2 Ophthalmology, The University of Texas Health Science Center at San Antonio; and the 3 Department of Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia.

PURPOSE. To determine the effect of light stress on retinal function and long-term photoreceptor viability in Royal College of Surgeons (RCS) rats and the applicability of the light treatment to the opsin P23H mutant rats.

METHODS. RCS rats at postnatal day (P)23 were illuminated with 120 foot-candles (fc) white light for 10 hours. Photoreceptor survival and basic fibroblast growth factor (bFGF) expression were measured at P60 and P83. Retinal function was evaluated by electroretinography. Opsin P23H transgenic rats were treated with light at P28 and analyzed at P70 for photoreceptor viability, ultrastructure, and bFGF expression.

RESULTS. Light-treated RCS rats at P60 had four to five rows of nuclei versus one to two rows in untreated littermates. The average amplitude of the ERG b-wave was 28 µV in treated rats, compared with 6 µV in untreated littermates. By P83 there was still significant preservation of the ONL in treated rats. Immunoblot analysis showed a high expression of bFGF in the treated retinas even 2 months after treatment. Illumination of P23H rats at P28 with 120 fc white light for 10 hours caused substantial photoreceptor cell death, although bFGF expression was upregulated. Lowered illumination dosages continued to cause photoreceptor damage until levels were reached that neither caused damage nor enhanced survival.

CONCLUSIONS. Although light stress promotes photoreceptor survival and function in the RCS rat, it elicits death signals in the P23H rats that may not be overcome by survival-promoting factors. Therefore, use of light stress to promote photoreceptor survival should be considered with regard to sensitivity of the mutation to light damage.




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