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Alteration in retinal pigment epithelium (RPE) results in the visual dysfunction and blindness of retinal degenerative diseases. Injection of sodium iodate (NaIO
3
) generates degeneration of RPE. We analyzed the sequential ultrastructure and expression of proliferating cell nuclear antigen (PCNA) and retina-specific RPE65 in NaIO
3
-induced retinal degeneration model. Adult male rats were injected 1% NaIO
3
(50 mg/kg) and eyes were enucleated at 1, 3, 5, 7 and 14 days post-injection (DPI), fixed, and processed for histological analysis. NaIO
3
-induced retinal degeneration was successfully established. At 1 DPI, most RPE cells were degenerated and replaced by a few proliferating RPE cells in the peripheral area. At 3 DPI, the RPE and photoreceptor out segments (POS) underwent a marked morphological change, including POS disruption, accumulation of residual bodies in RPE and POS, and hyperplasia of the RPE cell. At 5 DPI, POS showed a maximum increase in the outer segment debris and the retina showed partial detachment. These abnormal morphological changes gradually decreased by day 7. At 14 DPI, the damaged RPE and POS were partially regenerated from the peripheral to the central region. Expression of PCNA and RPE65 increased from day 3 onward. The damaged RPE showed earlier expression of PCNA and RPE65 than POS. The RPE damaged by NaIO
3
rapidly proliferated to put down roots on Bruch’s membrane from the peripheral retina and proliferation and hyperplasia of the RPE had a regular direction of progress. Therefore, NaIO
3
-induced acute changes in retina mimic the patho-morphologic features of RPE-related diseases.