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Tatsuro Ishibashi, MD, PhD; Toshinori Murata, MD, PhD; Masanori Hangai, MD, PhD; Ryoji Nagai, PhD; Seikoh Horiuchi, MD, PhD; Pedro F. Lopez, MD; David R. Hinton, MD; Stephen J. Ryan, MD

Arch Ophthalmol. 1998;116:1629-1632.

Objective  To investigate the localization of N-(carboxymethyl)lysine (CML), a component and major immunologic epitope of advanced glycation end products, in aged eyes and choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration.

Methods  Immunohistochemistry for CML was performed using 8 snap-frozen, surgically excised CNVMs. Twelve eyes from patients aged 69 to 82 years and 2 donor eyes, 1 each from a 23-week-old fetus and 21-year-old patient, without age-related macular degeneration or diabetic retinopathy were also examined. To determine if retinal pigment epithelial cells in CNVMs accumulate advanced glycation end products, cytokeratin and CML were stained in paired serial sections.

Results  Soft, macular drusen and/or basal laminar and basal linear deposits were observed in 8 of 12 aged eyes. Each case showed CML accumulation, while overlying retinal pigment epithelial cells showed no accumulation in all 12 eyes. In CNVMs, however, retinal pigment epithelial cells showed CML accumulation in their cytoplasm.

Conclusion  The additional accumulation of advanced glycation end products in soft, macular drusen and/or retinal pigment epithelial cells may play a role in the pathogenesis of CNVM formation in age-related macular degeneration.

Clinical Relevance  Recently, advanced glycation end products have been found to play a role both in aging changes and neovascularization. Localization of advanced glycation end products in the above-mentioned tissue may lead to a better understanding of the pathogenesis of age-related macular degeneration.

From the Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan (Dr Ishibashi); the Department of Biochemistry, Kumamoto University School of Medicine, Kumamoto, Japan (Drs Nagai and Horiuchi); the Department of Ophthalmology, Doheny Eye Institute (Drs Murata, Hangai, Lopez, and Ryan), and Department of Pathology (Dr Hinton), University of Southern California School of Medicine, Los Angeles; and Center for Excellence in Eye Care, Miami, Fla (Dr Lopez).

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