IMMUNOHISTOLOGIC STUDIES OF TYPE-IV COLLAGEN IN ANTERIOR LENS CAPSULES OF PATIENTS WITH ALPORT SYNDROME

BACKGROUND: Alport syndrome is an inherited disorder affecting the kid ney, eye and ear arising from mutations in the gene COL4A5, which enco des the alpha 5 chain of type IV collagen. Structural defects of glome rular basement membranes in Alport syndrome are associated in most ins tances with failure to detect the alpha 3, alpha 4, and alpha 5 chains of type IV collagen as well as the Alport antigen that is identified in normal tissues by a genetically discriminating alloantibody and mon oclonal antibody. Anterior lenticonus is an ocular abnormality pathogn omonic of Alport syndrome that is associated with marked thinning of t he anterior lens capsule (ALC). The reactivity of Alport ALC with type IV collagen antibodies has not previously been reported. EXPERIMENTAL DESIGN: ALCs were obtained at the time of cataract extraction from tw o unrelated males with Alport syndrome and anterior lenticonus, and st ained with antibodies against the alpha 1, alpha 2, alpha 3 and alpha 4 chains of type IV collagen, as well as an antibody against the alpha 5(IV) chain. Controls consisted of ALCs from a normal individual and from a patient with diabetes mellitus. RESULTS: Normal and diabetic AL Cs reacted with antibodies against the alpha 1, alpha 2, alpha 3, and alpha 4 chains of type IV collagen and the alpha 5(IV) chain. In one o f the Alport patients, ALC showed no reactivity with antibodies agains t the alpha 5(IV) chain and the alpha 3 and alpha 4 chains of type IV collagen. In the second patient, ALC reactivity with these antibodies was preserved. Epidermal basement membranes from this second patient a lso showed reactivity with antibody against the alpha 5(IV) chain, unl ike most males with Alport syndrome. In both Alport patients, ALCs rea cted with antibodies against the alpha 1(IV) and alpha 2(IV) chains. C ONCLUSIONS: These findings suggest that anterior lenticonus in patient s with Alport syndrome may be associated with absence of the alpha 3 a nd alpha 4 chains of type IV collagen, as well as the alpha 5(IV) chai n, from anterior lens capsule. On the other hand, these chains may be present in Alport patients with anterior lenticonus. The precise struc tural basis for mechanical weakness of the anterior lens capsule in pa tients with Alport syndrome remains to be determined.