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. Taken together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision, as well as optimal contrast detection and acuity.
Dopamine (DA) functions as an essential neuromodulator in the brain and retina such that disruptions in the dopaminergic system are associated with common neurologic disorders such as Parkinson's disease. Although a reduction in DA content has been observed in diabetes, its effects in the development of diabetes-induced neuropathy remains unknown. Because the retina is rich in DA and has a well known diabetes-induced pathology (diabetic retinopathy or DR), this study was designed to examine the role of retinal DA deficiency in early visual defects in DR. Using rodent models of type 1 diabetes mellitus, we investigated whether diabetes caused a reduction in retinal DA content in both rats and mice and determined whether restoring DA levels or activating specific DA receptor pathways could improve visual function (evaluated with optokinetic tracking response) of diabetic mice, potentially via improvement of retinal function (assessed with electroretinography). We found that diabetes significantly reduced DA levels by 4 weeks in rats and by 5 weeks in mice, coincident with the initial detection of visual deficits. Treatment with L-DOPA, a DA precursor, improved overall retinal and visual functions in diabetic mice and acute treatment with DA D1 or D4 receptor agonists improved spatial frequency threshold or contrast sensitivity, respectively. Together, our results indicate that retinal DA deficiency is an underlying mechanism for early, diabetes-induced visual dysfunction and suggest that therapies targeting the retinal dopaminergic system may be beneficial in early-stage DR.
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.
A 54-year-old woman presented with a 2-year history of a slow-growing subcutaneous nodule of the medial right lower eyelid adjacent to the inferior canaliculus. The patient reported right-sided epiphora suggesting lacrimal outflow obstruction. The surgically excised nodule was consistent with a chondroma. A rare tumor, soft tissue chondroma, is most often seen in the extremities, but has also been observed in the head and neck region. To their knowledge, this is the first reported case of a soft tissue chondroma of the eyelid.
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