Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 44, Issue 10, Pages 4505-4514Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.03-0453
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- NEI NIH HHS [P30 EY012190, EY12190, R01 EY010609, EY10609, R56 EY010609, P30 EY012190-02, R01 EY010609-07] Funding Source: Medline
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PURPOSE. To evaluate the effects of INS37217 on the recovery of retinal function after experimental retinal detachment induced by subretinal injection. METHODS. Subretinal injections of 1 muL of fluorescent microbeads, saline, or INS37217 (1-200 muM) were made by the transvitreal method in normal (C57BL/6) mice and in mice heterozygous for the retinal degeneration slow (rds) gene. Control, mock-injected animals underwent corneal puncture without injection. Histologic and ERG evaluations were made at 0 to 1 and 8 hours, and 1, 3, 7, 10, 14, and 60 days post injection (PI). DNA fragmentation was evaluated by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL). RESULTS. A single subretinal injection of saline solution containing fluorescent beads caused a histologically evident retinal detachment and distributed the microbeads to almost all the subretinal space. Spontaneous reattachment occurred within 24 hours after injection and was accompanied by evident retinal folding that appeared largely resolved by 6 days later. Relative to controls, injection of saline resulted in approximately 40% recovery of dark-adapted a-wave amplitude at 24 hours PI and gradually improved to approximately 90% of controls at 2 months PI. Subretinal injection of saline containing INS37217 (10 muM) significantly increased rod and cone ERG of normal and rds(+/-) mice at 1 and 10 days PI, when compared with injection of saline alone. Additionally, INS37217 reduced the number of TUNEL-positive photoreceptors and the enhanced rate of reattachment. CONCLUSIONS. Enhancement of ERG recovery by INS37217 is likely due to reduced retinal folding and cell death associated with detachment. These results support the use of INS37217 to help restore function after therapies that involve subretinal administration of drugs in animal models of retinal diseases.
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