Fazila Aseem

Retinal Dopamine Mediates Multiple Dimensions of Light-Adapted Vision

Dopamine is a key neuromodulator in the retina and brain that supports motor, cognitive, and visual function. Here, we developed a mouse model on a C57 background in which expression of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, is specifically disrupted in the retina. This model enabled assessment of the overall role of retinal dopamine in vision using electrophysiological (electroretinogram), psychophysical (optokinetic tracking), and pharmacological techniques. Significant disruptions were observed in high-resolution, light-adapted vision caused by specific deficits in light responses, contrast sensitivity, acuity, and circadian rhythms in this retinal dopamine-depleted mouse model. These global effects of retinal dopamine on vision are driven by the differential actions of dopamine D1 and D4 receptors on specific retinal functions and appear to be due to the ongoing bioavailability of dopamine rather than developmental effects. Together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision as well as optimal contrast detection and acuity.

Visually-Driven Ocular Growth in Mice Requires Functional Rod Photoreceptors

PURPOSE Proper refractive eye growth depends on several features of the visual image and requisite retinal pathways. In this study, we determined the contribution of rod pathways to normal refractive development and form deprivation (FD) myopia by testing Gnat1(-/-) mice, which lack functional rods due to a mutation in rod transducin-α. METHODS Refractive development was measured in Gnat1(-/-) (n = 30-36) and wild-type (WT) mice (n = 5-9) from 4 to 12 weeks of age. FD was induced monocularly from 4 weeks of age using head-mounted diffuser goggles (Gnat1(-/-), n = 9-10; WT, n = 7-8). Refractive state and ocular biometry were obtained weekly using a photorefractor, 1310 nm optical coherence tomography, and partial coherence interferometry. We measured retinal dopamine and its metabolite, DOPAC, using HPLC. RESULTS During normal development, the refractions of WT mice started at 5.36 ± 0.68 diopters (D) and became more hyperopic before plateauing at 7.78 ± 0.64 D. In contrast, refractions in Gnat1(-/-) mice were stable at 7.39 ± 1.22 D across all ages. Three weeks of FD induced a 2.54 ± 0.77 D myopic shift in WT mice, while Gnat1(-/-) mice did not respond to FD at any age. Axial lengths of Gnat1(-/-) and WT mice increased with age, but differences between genotypes or with goggling did not reach statistical significance and fell within the precision of the instruments. The DOPAC levels were significantly lower in Gnat1(-/-) mice from 2 to 12 weeks of age with DOPAC/dopamine ratio peaking earlier in Gnat1(-/-) compared to WT mice. No differences in dopamine were seen in response to FD or between genotypes. CONCLUSIONS Functional rod photoreceptors are critical to normal refractive development and the response to FD in mice. Dopamine levels may not directly modulate the refractive state of the mouse eye, but tonic levels of dopamine during development may determine susceptibility to myopia.