Submacular DL-alpha-Aminoadipic Acid Eradicates Primate Photoreceptors but Does Not Affect Luteal Pigment or the Retinal Vasculature

PURPOSE. Macular telangiectasia type 2 (MT2) is a condition of uncertain etiology characterized by retinal vascular abnormalities, depletion of luteal pigment, and photoreceptor loss. To model this condition, the authors recently used a purportedly glial-selective toxin, DL-alpha-aminoadipic acid (DL-alpha-AAA), to test the effect of Muller cell disruption on the blood-retinal barrier in rats. In this study, they investigated macular changes after subretinal injection of DL-alpha-AAA in monkeys. METHODS. Various doses of DL-alpha-AAA were injected beneath the macula in eight monkey eyes. Eyes were examined by multifocal electroretinography (mfERG), optical coherence tomography (OCT), fundus autofluorescence, color photography, and fluorescein angiography. Five months after injection, eyes were examined by histology and immunohistochemistry for changes in photoreceptors and the retinal glia. In vitro studies evaluated the effect of DL-alpha-AAA on 661W cone photoreceptor viability. RESULTS. Subretinal injection of DL-alpha-AAA resulted in virtually complete ablation of photoreceptors in the injected area, as shown by OCT and histology, and severely impaired mfERG responses. Muller cells, albeit activated, survived the injury. Macular pigment remained unchanged in the central fovea. Subretinal injection of DL-alpha-AAA did not induce vascular leakage, though it increased the fundus autofluorescence. DL-alpha-AAA had a dose-dependent toxic effect on 661W photoreceptors. CONCLUSIONS. Submacular injection of DL-alpha-AAA induced severe damage to photoreceptors but failed to eliminate Muller cells in monkeys. Central macular pigment persisted despite loss of photoreceptors, and the retinal vasculature was unaffected. These observations may have significance in studying the roles of different cellular components in the pathogenesis of MT2. (Invest Ophthalmol Vis Sci. 2011; 52: 119-127) DOI: 10.1167/iovs.10-6033