C57BL/6J, DBA/2J, and DBA/2J.Gpnmb+ mice have different visual signal processing in the inner retina

PURPOSE To characterize differences in retinal ganglion cell (RGC) function in mouse strains relevant to disease models. C57BL/6J (B6) and DBA/2J (D2) are the two most common mouse strains; D2 has two mutated genes, tyrosinase-related protein 1 (Tyrp1) and glycoprotein non-metastatic melanoma protein B (Gpnmb), causing iris disease and intraocular pressure (IOP) elevation after 6 months of age that results in RGC degeneration, and is the most widely used model of glaucoma. DBA/2J.Gpnmb(+) (D2.Gpnmb(+)) is the wild type for the Gpnmb mutation and does not develop IOP elevation and glaucoma. METHODS Young (2-4 months of age) B6, D2, and D2.Gpnmb(+) mice (n=6 for each group) were tested with pattern electroretinogram (PERG) in response to different contrasts and spatial frequencies. PERG amplitude and latency dependencies on stimulus parameters (transfer functions) were established for each mouse strain, together with corresponding thresholds for contrast and spatial resolution. RESULTS PERG analysis showed that B6, D2, and D2.Gpnmb(+) mice had comparable contrast threshold and spatial resolution. Suprathreshold spatial contrast processing, however, had different characteristics in the three strains. PERG amplitude and latency changes with increasing contrast were different between B6 and D2 as well as between D2 and D2.Gpnmb(+). CONCLUSIONS B6, D2, and D2.Gpnmb(+) mice have different characteristics of PERG spatial contrast processing consistent with different mechanisms of contrast gain control. This may imply differences in the activity of underlying PERG generators and synaptic circuitry in the inner retina.