April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Retinal Changes After Subretinal Injection of DL--Aminoadipic Acid in Non-Human Primates
W. Shen; J. Zhang; Y. Hu; S. Chung; S. Li; M. C. Gillies
Author Affiliations & Notes
  • W. Shen
    Clinical Ophthal & Eye Hlth, University of Sydney, Sydney, Australia
  • J. Zhang
    Peking University Eye Center, Peking University, Beijing, China
  • Y. Hu
    Peking University Eye Center, Peking University, Beijing, China
  • S. Chung
    Clinical Ophthal & Eye Hlth, University of Sydney, Sydney, Australia
  • S. Li
    Clinical Ophthal & Eye Hlth, University of Sydney, Sydney, Australia
  • M. C. Gillies
    Clinical Ophthal & Eye Hlth, University of Sydney, Sydney, Australia
  • Footnotes
    Commercial Relationships  W. Shen, None; J. Zhang, None; Y. Hu, None; S. Chung, None; S. Li, None; M.C. Gillies, None.
  • Footnotes
    Support  Lowy Medical Research Institute
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 6226. doi:
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      W. Shen, J. Zhang, Y. Hu, S. Chung, S. Li, M. C. Gillies; Retinal Changes After Subretinal Injection of DL--Aminoadipic Acid in Non-Human Primates. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6226.

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Abstract

Purpose: : Macular telangiectasis (MacTel) is characterized by central depletion of macular pigment, superficial retinal crystalline deposits, intra-retinal vascular abnormalities, disturbance to photoreceptors and intraretinal cavitation. Currently, the pathogenesis of MacTel is entirely unknown. Our previous study showed that subretinal injection of DL--aminoadipic acid (DL-AAA), a glial toxin, induced retinal vascular telangiectasis in rats (2008 ARVO#3973/D863). This study aimed to investigate whether DL-AAA induces similar changes in monkeys.

Methods: : The effect of DL-AAA on retinal pigment epithelium (RPE), retinal vascular endothelial cells, pericytes, Müller cells (rMC-1) and photoreceptors (661w cell line), was evaluated in vitro. Fifty microlitter of DL--AAA (5, 10 or 50 mM) or balanced salt solution (BSS) was injected subretinally into the macular region in 8 eyes of 4 monkeys. Injected eyes were examined by optical coherence tomography, multifocal electroretinography, fundus autofluorescence, fundus colour photography and fluorescein angiography (FFA) between 2 weeks and 5 months post injection. At 5 months post injection, eyes were enucleated for changes in histology and glial biomarkers of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP).

Results: : DL-AAA showed dose-dependent toxic effect on Müller cells and photoreceptors in vitro. After DL-AAA injection in monkeys, severe photoreceptor damage were observed from 2 weeks post injection of DL-AAA but these changes were not observed in BSS injected eyes. FFA demonstrated a normal pattern of central macular pigment. Neither macular vascular leakage nor telangiectasis was observed after DL-AAA injection. Fundus colour photography and autofluorescence indicated persistence of the central luteal pigment for up to 5 months after the central photoreceptors had been destroyed. Histology revealed severe damage to photoreceptors by DL-AAA. However, immunostaining for GS and GFAP demonstrated only slight disturbance of Müller cells in the DL-AAA injected area.

Conclusions: : Damage to photoreceptors in the central macular region does not induce central macular pigment depletion and vascular abnormalities. These observations may have clinical significance in investigation of the pathogenesis of MacTel.

Keywords: macula/fovea • photoreceptors • Muller cells 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
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