An unusual retinal vascular morphology in connection with a novel AIPL1 mutation in Leber's congenital amaurosis

Abstract

Aims: To report a case of an unusual retinal vascular morphology in connection with a novel AIPL1 mutation in a patient with Leber's congenital amaurosis (LCA).

Methods: A patient with LCA and no light perception from birth had both eyes enucleated at the age of 22 years because of excruciating pain. Mutation analysis was performed on known LCA genes. The eyes were processed for casts of the vascular tree, routine histopathology, and electron microscopy.

Results: A novel H82Y (244C-->T) mutation and a H90D (286G-->C) polymorphism were detected in exon 2 of the AIPL1 gene. Both the cast and the histopathological examination showed dilated retinal vessels, mainly venules, primarily localised in the posterior pole. In the mid-peripheral retina the density of capillaries on the arteriolar side of the microcirculatory units was significantly decreased. The vascular system was seen to gradually attenuate towards the retinal periphery, and to stop at a zone located approximately 4 mm from the ora serrata along the whole circumference. In this zone pigmented aggregates characteristic of retinitis pigmentosa were seen to ensheath the retinal vessels. The photoreceptors were almost totally absent and retinal gliosis was present. A decreased number of ganglion cells and an increased vacuolisation of the nerve fibre layer were observed. The retinal pigment cells and Bruch's membrane appeared normal in all regions.

Conclusion: An unusual retinal vascular morphology in an LCA patient is presented and possible pathogenic mechanisms of the findings are discussed.

Figure 1

Part of the lower temporal arcade (large horizontal vessels in the middle of the image). The venules display pronounced tortuosity. The capillary density is high, including the radial peripapillary network (bar = 500 μm).

Figure 2

Higher magnification of the vessels radiating towards the periphery. The vascular density increases from the arteriolar (A) to the venular (V) side of the microcirculatory units (bar = 50 μm).

Figure 3

Nasal retina of the right eye. The vessels terminate (arrows) at an avascular zone approximately 4 mm wide at the ora serrata (bar = 1 mm).

Figure 4

Vessels near the peripheral avascular zone are ensheathed by lines of pigment (arrows) (bar = 500 μm).

Figure 5

(A) Histological section of retina with abnormal, dense vascular meshwork. Survey. Asterisks on markedly dilated vessels. Arrow on black cast material in a minor arteriole (HE, ×100). (B) Higher magnification demonstrating an area also rich in minor vessels. Marking as in (A) (HE, ×200).