title: Submacular DL-alpha-aminoadipic acid eradicates primate photoreceptors but does not affect luteal pigment or the retinal vasculature.
abstract: OBJECTIVE
  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-α-aminoadipic acid (DL-α-AAA), to test the effect of Müller cell disruption on the blood-retinal barrier in rats. In this study, they investigated macular changes after subretinal injection of DL-α-AAA in monkeys.
  
  
  METHODS
  Various doses of DL-α-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-α-AAA on 661W cone photoreceptor viability.
  
  
  RESULTS
  Subretinal injection of DL-α-AAA resulted in virtually complete ablation of photoreceptors in the injected area, as shown by OCT and histology, and severely impaired mfERG responses. Müller cells, albeit activated, survived the injury. Macular pigment remained unchanged in the central fovea. Subretinal injection of DL-α-AAA did not induce vascular leakage, though it increased the fundus autofluorescence. DL-α-AAA had a dose-dependent toxic effect on 661W photoreceptors.
  
  
  CONCLUSIONS
  Submacular injection of DL-α-AAA induced severe damage to photoreceptors but failed to eliminate Müller 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.
authors: Save Sight Institute, University of Sydney, Australia. shenw@med.usyd.edu.au
authors: Weiyong
authors: W
authors: Shen
authors: Jun
authors: J
authors: Zhang
authors: Sook Hyun
authors: SH
authors: Chung
authors: Yuntao
authors: Y
authors: Hu
authors: Zhizhong
authors: Z
authors: Ma
authors: Mark C
authors: MC
authors: Gillies
mesh_terms: D015074:2-Aminoadipic Acid / Q000633:toxicity*; D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005451:Fluorescein Angiography; D014975:Lutein / Q000378:metabolism*; D008251:Macaca; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D010781:Photography; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D055351:Retinal Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects*; D041623:Tomography, Optical Coherence; D024341:Xanthophylls / Q000378:metabolism*; D065146:Zeaxanthins
chemical_list: D018691:Excitatory Amino Acid Antagonists; D024341:Xanthophylls; D065146:Zeaxanthins; D015074:2-Aminoadipic Acid; D014975:Lutein