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Age-Related Retinal Pigment Epithelium and Bruch’s Membrane Degeneration in Senescence-Accelerated Mouse

From the Wilmer Ophthalmological Institute, The Johns Hopkins University, School of Medicine, Baltimore, Maryland.

PURPOSE. To investigate age-related changes in the retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in the senescence-accelerated mouse (SAM).

METHODS. The external and eyecup features and light and electron microscopic findings were examined in three male and two female mice of a senescence-prone mouse strain (SAM P₈) monthly for 12 months. These results were compared with those in age-matched mice of similar background but senescence resistant (SAM R₁). Choroidal vascular casts were prepared at 12 months in seven mice each of the SAM P₈ and SAM R₁ strains. Quantitative analysis of area of choriocapillaris was performed by automated image analysis, and the results were analyzed by paired Student’s t-test.

RESULTS. We found in the SAM P₈ strain that hair loss, coarseness of hair texture, and ulceration of skin appeared and increased as the age advanced (at approximately 5–9 months). Eyecup examination showed no differences. Light and electron microscopy revealed progressively more prominent abnormalities in the RPE and Bruch’s membrane mice older than 10 months. Two of the five SAM P₈ mice older than 11 months showed what appeared to be intra-Bruch’s membrane choroidal neovascularization. The RPE and Bruch’s membrane appeared normal in the SAM R₁ strain. In the SAM P₈, vascular casts of the choriocapillaris showed a mild but significant decrease in vascular area when compared with the SAM R₁ strain at 12 months (P = 0.011).

CONCLUSIONS. Senescence accelerated mice develop progressive age-related changes in the RPE–Bruch’s–choriocapillaris complex that have features that may be relevant in the study of age-related macular changes in humans.

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