Retinal basement membrane abnormalities and the retinopathy of Alport syndrome

• Published in: Investigative ophthalmology & visual science Vol. 51; no. 3; pp. 1621 - 1627
• Main Authors: Savige, Judy, Liu, John, DeBuc, Delia Cabrera, Handa, James T, Hageman, Gregory S, Wang, Yan Yan, Parkin, John D, Vote, Brendan, Fassett, Rob, Sarks, Shirley, Colville, Deb
• Format: Journal Article
• Language: English
• Published: United States Association for Research in Vision and Ophthalmology, Inc 01-03-2010
• Subjects: Adolescent; Adult; Aged; Autoantigens - metabolism; Basement Membrane - metabolism; Basement Membrane - pathology; Bruch Membrane - ultrastructure; Collagen Type IV - metabolism; Female; Genetic Linkage; Humans; Immunoenzyme Techniques; Male; Middle Aged; Nephritis, Hereditary - complications; Nephritis, Hereditary - diagnosis; Nephritis, Hereditary - metabolism; Nerve Fibers - pathology; Retina - pathology; Retinal Diseases - diagnosis; Retinal Diseases - etiology; Retinal Diseases - metabolism; Retinal Pigment Epithelium - metabolism; Tomography, Optical Coherence; Young Adult
• ISSN: 0146-0404; 1552-5783
• DOI: 10.1167/iovs.08-3323

To determine the effects of X-linked and autosomal recessive Alport syndrome on retinal basement membranes and how these result in the characteristic perimacular dot-and-fleck retinopathy, lozenge, and macular hole.
The type IV collagen chains present in the normal retina were determined immunohistochemically. Ten patients with Alport syndrome underwent retinal photography and optical coherence tomography to determine the thickness of the internal limiting membrane (ILM) by segmentation analysis, the layers affected by the retinopathy, and any correlates of the lozenge and macular hole. Bruch's membrane was examined directly by electron microscopy in a donated Alport eye.
The alpha3alpha4alpha5 type IV collagen network was present in the normal ILM and in the retinal pigment epithelium basement membrane of Bruch's membrane. In Alport syndrome, the ILM/nerve fiber layer and Bruch's membrane were both thinned. The dot-and-fleck retinopathy corresponded to hyperreflectivity of the ILM/nerve fiber layer in the distribution of the nerve fiber layer. The lozenge and macular hole corresponded to temporal macular thinning. The thinning across the whole retina was principally due to thinning of the ILM/nerve fiber layer and inner nuclear layer.
The Alport dot-and-fleck retinopathy results primarily from abnormalities in the ILM/nerve fiber layer rather than in Bruch's membrane. Thinning of the ILM/nerve fiber layer contributes to the retinopathy, lozenge, and macular hole, possibly through interfering with nutrition of the overlying retina or clearance of metabolic by-products.