Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 103

Retinal degeneration is the most common manifestation of ciliary dysfunction in the eye, although coloboma and microphthalmia can occur in some ciliopathies as a result of defective HH signaling. In the retinal photoreceptor cells, modified primary cilia form the photoreceptor outer segments and express proteins that are specialized for phototransduction. The outer segments are specialized sensory cilia, and deficient morphogenesis and/or dysfunction of these sensory cilia caused by mutations in a wide range of photoreceptor‐specific and ciliary genes can result in inherited retinal degenerations [53]. Almost all of the proteins involved in maintenance of the outersegment and phototransduction (most notably rhodopsin) are synthesized in the inner segment and must be transported to the outer segment via the connecting cilium. As a result, the efficient transport of cargo along the connecting cilium is essential for the assembly and maintenance of the photoreceptor outer segment. Mutations in several genes that encode proteins localized to the connecting cilium and/or its basal body can disrupt this process of intersegmental transport and result in the mislocalization of outer segment proteins and disorganization of the outer segments [54–58], which often precedes photoreceptor degeneration [59, 60]. In addition, the axoneme of the connecting cilium extends into the OS and is thought to establish the proper alignment of the membranous disks containing rhodopsin and other proteins required for phototransduction [61].

Histology is a very sensitive and specific method for detecting retinopathies. In normal mouse eyes, subretinal macrophages are absent or very rare, the inner and outer segments of the photoreceptors appear in organized columns and are of approximately equal length, and the outer nuclear layer is thicker than the inner nuclear layer. Almost all disruptions affecting the development or function of outer segments will lead to degeneration of photoreceptors, which can be detected histologically even at early stages by the appearance or any combination of the following changes: increased numbers of subretinal macrophages (Figure 6.6), disrupted/thin outer segments, or reduced thickness of the outer nuclear layer (consisting of photoreceptor nuclei; Figure 6.7).

Figure 6.6 Eye. Macrophages within the outer segment of photoreceptor are present at the earlier stages of retinal degeneration.