In–vivo Retinal Imaging and Anatomical Findings in Aged Animals Lacking the Gene for Complement Factor–H

Abstract

Purpose: : To evaluate the effect of complement Factor–H gene knockout on mouse retinal structure using high–resolution non–invasive retinal imaging and histology.

Methods: : The retinae from 2 year old transgenic mice lacking the complement factor–H (CFH) gene, and age–matched controls, were imaged non–invasively using a high resolution confocal scanning laser ophthalmoscope (cSLO). Briefly, animals were anaesthetised, the pupil was dilated, and colour fundoscopy pictures were also taken prior to cSLO. Following in vivo imaging, animals were terminated and eyes were prepared and processed for light and electron microscopy, immunocytochemistry and conventional histopathology. Analysis of retinal structure was undertaken using histochemical, immunohistochemical and ultrastructural techniques to detect potential pathological changes.

Results: : Fundoscopy pictures revealed deposits in both CFH deficient mice and age–matched controls. In controls, however, the deposits were mainly confined to the neural retina, whereas in CFH deficient mice very few deposits were seen within the neural retina but were subretinal apposing pigmented cells. cSLO revealed the presence of autofluorescent deposits in both groups of animals. Again, in age–matched controls, the deposits were mainly confined to the neural retina. Conversely, in CFH deficient animals the autofluorescent deposits were detected primarily in the subretinal space/Bruch’s membrane region. cSLO imaging in CFH deficient animals also indicated a possible thinning of the nerve fibre layer. The most consistent finding on histological examination was the presence of reduced sub–retinal pigment epithelium deposit accumulation in the CFH deficient animals.

Conclusions: : CFH deficient animals exhibit a retinal pathology which is distinct from that of age–matched controls and which cannot be accounted for by aging alone.

Keywords: age-related macular degeneration • transgenics/knock-outs • degenerations/dystrophies