Cone degeneration in aging and age-related macular degeneration

Objective: To examine the morphological features of macular photoreceptors in histologically normal retina from normal donor eyes and eyes with age-related macu- lar degeneration (AMD). Methods: The macular region was excised from 18 donor eyes (aged 22-96 years) and cryosectioned. Sections were stained with hematoxylin-eosin or double immu- nolabeled using opsin antibodies or synaptic markers. Results: Three of 8 retinas studied in detail had AMD lesions; the remainder were histologically normal. Im- munoreactivity to cone opsin was abnormal in parts of all retinas (3.5%-95.0% of each sample) and was associated with swelling of and altered immunoreactivity in the cone distal axon. In non-AMD retinas, the anomalies were mainly in nonfoveal macular locations. The nature of the anomalies was identical in non-AMD retinas and in parts of AMD retinas adjacent to overt degeneration. Conclusion: Redistribution of opsin and anomalies in the distal cone axon are common in the aging human macula and may indicate susceptibility to AMD. Clinical Relevance: The findings are consistent with tests of cone function in aging and early AMD, which suggests that integrated cone functions-including contrast sensitivity, color matching, and short wavelength- sensitive cone sensitivity-are the most reliable prognostic indicators of progression in AMD.