APOPTOSIS OF PHOTORECEPTOR CELLS IN ORNITHINE-INDUCED RETINOPATHY

Background: The intravitreal injection of ornithine produces selective damage to the retinal pigment epithelium (RPE) and results in a loss of RPE, choriocapillaris and photoreceptor cells. To elucidate the mec hanism of secondary retinal atrophy, we investigated the presence of a poptotic cells in a rat model of ornithine-induced retinopathy. Method s: At 6 and 12 h and 1, 2, 4, 7, 14 and 28 days after an intravitreal injection of L-ornithine hydrochloride in rat eyes, we removed the eye s and subjected them to histopathological examination. We detected apo ptotic cells by terminal deoxynucleotidyl transferase-mediated deoxyur idine triphosphate digoxigenin nick end labeling (TUNEL) assay, which stains the 3'-OH ends of fragmented DNA. We used electron microscopy t o detect the apoptotic cells morphologically. Results: RPE cells were selectively damaged immediately after ornithine administration. TUNEL- positive photoreceptor cells appeared exclusively in the photoreceptor cell layer 12 h after ornithine administration. The number of TUNEL-p ositive cells increased throughout the 2 days following the injection, then decreased markedly. TUNEL-positive cells remained until 28 days, when the photoreceptor cells had disappeared. The ganglion cell layer , inner nuclear layer and damaged RPE cells were negative for TUNEL st aining during all stages. The electron microscopic study also revealed the pyknotic nuclei of apoptotic photoreceptor cells. Conclusion: An intravitreal injection of ornithine caused primary damage to the RPE, and subsequently some of the photoreceptor cells revealed apoptosis by TUNEL assay. These findings suggest the dysfunction of the RPE causes photoreceptor cell death according to the intrinsic program of an apo ptotic mechanism.