Histologic and biochemical evaluation of three eyes with Autosomal Dominant Neovascular Inflammatory...

Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare inherited retinal disease caused by mutations in CAPN5. We report clinicopathologic and histologic findings from donor eyes representing multiple stages of ADNIV, including early-stage disease, and evaluate calpain-5 (CAPN5) expression and localization in affected tissue.

Histopathologic staining and immunofluorescence were performed on eyes from three patients with genetically confirmed ADNIV (stages II, IV, and V). Labeling targeted glial, immune, and vascular markers, as well as CAPN5 distribution. Western blotting of aqueous- and detergent-soluble fractions was performed on retinal and RPE/choroid tissue from the stage II donor and an age- and sex-matched control. Clinical history from the stage IV donor was reviewed.

All three ADNIV eyes in this series demonstrated lymphocytic infiltration predominantly confined to the choroid. The stage II eye showed preserved retinal organization with early Müller cell gliosis and microglial activation. Later stages exhibited neuroretinal disorganization and fibrovascular encapsulation. RPE preservation was noted in all 3 eyes. CAPN5 was expressed throughout retinal and choroidal tissues. Western blot and fractionation analysis of the stage II eye showed no difference in CAPN5 abundance or distribution compared with control tissue.

These findings support a disease process characterized by early choroidal inflammation and progressive retinal degeneration in ADNIV. Stable CAPN5 localization in early disease suggests that pathogenic effects may arise from altered mutant protease activity rather than from changes in protein abundance or localization. Recognition of early inflammatory changes may inform future diagnostic and therapeutic approaches in this rare condition.