Myopia is a substantial public health challenge worldwide. It affects more than 80% of the population of Hong Kong and more than 40% of individuals over the age of 12 years in the United States. Although it is well established that defocused images alter eye growth and ocular refraction, the mechanism, and effects of defocused images on the signaling of retinal ganglion cells (RGCs) that contribute to either emmetropization or refractive error remain unknown. Therefore, the responses of populations of RGCs in dark-adapted mouse retinas to the projection of defocused images of different dioptric powers and spatial frequencies were recorded using a 256 channel Multi-Electrode Array (MEA). The retina could reflect the projected image, leading to a dramatic change in the firing pattern when presented with the defocused image. The responses of RGCs were also affected by the application of dopamine D1 and D2 receptor antagonists and agonists. In addition, when defocused images were projected, the synchrony firing patterns between the OFF-Delayed RGCs with other delayed response RGCs or displaced amacrine cells (ACs) were lost, which may be related to edge detection. The results suggest that defocused images could change the multineuronal firing pattern in the mouse retina. Such a change in the population of RGC activities may serve as an early step in myopia development in the retina. Gap junctions play important functional roles, such as signal averaging, noise reduction, and neuronal synchronization to code fundamental visual information in the retinal circuit. Modulation of gap junctions contributes to retinal plasticity, which enables the retina to adapt to visual inputs as self-adjusting neuronal networks. AII ACs coupled by connexin36 (Cx36) are actively modulated through phosphorylation at serine 293 via dopamine in the mouse retina. Therefore, insight into the regulation of Cx36 function is important to understand the visual signaling processes in both the normal and myopic retina. Form deprivation mouse myopia models were used to evaluate the expression patterns of Cx36-positive plaques (structural assay) and the state of Cx36 phosphorylation (functional assay) in AII ACs. The results showed increased Cx36 phosphorylation in the myopic retina compared to the normal control animals, but there was no change in the expression of Cx36. The results indicate increases in the functional gap junction coupling of AII ACs in the myopic retina, a mechanism that potentially adjusts to alter the noisy signal condition. In summary, this study showed that the population of RGCs/displaced ACs in the retina can respond differently to focused and defocused images and increases in the functional gap junction coupling of AII ACs in the myopic retina. These findings may be the basis for the proposed retina-to-sclera signaling pathway. Retinal signaling might be the first and the most important step in triggering myopia and may also serve as a continuous key signal in myopia development.
|Date of Award||22 Dec 2020|
- The Hong Kong Polytechnic University
|Supervisor||Chi Wai Do (Co-supervisor), Feng Pan (Supervisor), Feng Pan (Supervisor) & Chi Wai Do (Supervisor)|