Energy Depletion Hypothesis for Retinitis Pigmentosa
Enormous advances have been made in our understanding of human retinal degenerations, eg., numerous gene defects that cause retinitis pigmentosa (RP) have been identified and shown in many cases to encode photoreceptor cell proteins that participate in phototransduction (Clarke et al., 2000; Phelan and Bok, 2000; Pugh and Lamb, 2000). Although RP is genetically heterogeneous, the similar phenotype of typical RP (disturbed dark adaptation that progresses to night blindness, then complete blindness) has led researchers to speculate about a common underlying pathological mechanism. The equivalent light hypothesis for RP, formulated because constant or excessive light can cause photoreceptor degeneration in animals, has received some experimental support (Fain and Lisman, 1999). The pathological defect in RP has also been suggested to result from disturbance of the cytoskeletal systems in photoreceptor outer segments (OS) (Eckmiller, 1997), more specifically from disturbance of the special microtubulecontaining cytoskeletal system at the multiple incisures in many rod OS (Eckmiller, 2000). For unknown reasons, rods are more susceptible than cones to degeneration by both light and gene mutation. It is particularly puzzling that gene defects in myosin VIIa cause Usher syndrome (RP with hearing and vestibular defects) in humans but do not cause visual disturbances or blindness in mice or zebrafish (Gibson et al., 1995; Weil et al., 1995; Ernest et al., 2000). This puzzle has not been clarified by studies showing that myosin VIIa is localized in rodent rods and cones at the base of the ciliary axoneme, where it participates in transporting proteins (eg., opsin) into the OS (Liu et al., 1999).
KeywordsRetinitis Pigmentosa Outer Segment Bright Light Night Blindness Photoreceptor Outer Segment
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