Photoreceptor Oxidative Damage in Sympathetic Ophthalmia

Purpose

To determine photoreceptor oxidative stress and damage in sympathetic ophthalmia (SO).

Design

Immunohistologic study.

Methods

Eight formalin-fixed and paraffin-embedded human globes with typical histologic features of SO and five age-matched globes without intraocular inflammation (controls) were retrieved from the Doheny Eye Institute ophthalmic pathology files. Deparaffinized sections of the globes were processed to localize tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor-1 (TNF-R1), acrolein, inducible nitric oxide synthase (iNOS), and nitrotyrosine by immunolocalization method. The latter two were localized to photoreceptor mitochondria using anti–cytochrome C antibody. Apoptotic cells were detected by Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) assay and were localized to the site of oxidative stress using antinitrotyrosine antibody.

Results

Increased expression of TNF-α can be seen in the photoreceptor nuclear layer in all SO globes, whereas no such expression was observed in control globes. TNF-R1, iNOS, acrolein, and nitrotyrosine were immunolocalized to the inner segments of the photoreceptors in all SO globes, but only mild focal staining was observed in the control retinas. Both nitrotyrosine and iNOS immunolocalization revealed positive staining restricted primarily to mitochondria at the inner segments of the photoreceptors. Most of the TUNEL-positive cells were detected in the photoreceptors at the site of nitrotyrosine staining. In contrast, the age-matched control globes showed negative results.

Conclusions

In SO, photoreceptor mitochondrial oxidative stress occurs in the absence of leukocytic infiltration of the retina and may lead to photoreceptor apoptosis and subsequent vision loss. The oxidative stress seems to be mediated by iNOS and TNF-α. The current anti-inflammatory therapy combined with agents that could prevent oxidative stress may prevent photoreceptor damage in SO and may preserve vision.