| Author: | So, Chung Him |
| Title: | Exploring retinal neuron responses to defocused images in the mouse retina |
| Advisors: | Pan, Feng (SO) Tse, Dennis (SO) |
| Degree: | Ph.D. |
| Year: | 2024 |
| Subject: | Myopia Retinal ganglion cells Optic nerve -- Cytology Hong Kong Polytechnic University -- Dissertations |
| Department: | School of Optometry |
| Pages: | 180 pages : color illustrations |
| Language: | English |
| Abstract: | Purpose Although myopia, or nearsightedness, is a health problem worldwide, the mechanisms of its development remain unknown. It is hypothesized that refractive errors could result from the impact of defocused visual signals on various types of retinal neurons. This research study aimed to explore whether defocused images influence the signaling processes of individual types of retinal ganglion cells, specifically alpha retinal ganglion cells (αRGCs), as well as dopaminergic Amacrine Cells (Dopaminergic ACs), AII ACs, and Horizontal Cells (HCs). Additionally, the study examined the role of connexin 36 gap junctions (Cx36 GJs) in modulating these effects. Methods Several strains of mice, C57BL/6, KCNG-YFP, EGR-1, Fam81a, and Cx36-knockout, were used in this study. A custom-made device was used to project defocused images onto the retina under the microscope. Mightex 1000 generated light bars, annulus, and spots of varying sizes. Biophysical response of αRGCs, DACs, AII ACs, and HCs were recorded by patch clamp in flat-mounted retinas. Intracellular dye injection and confocal microscopy were then applied to confirm and study the morphology of neurons in the mouse retinas. The Generalized linear model (GLM) was used to predict RGC responses in normal and lens-induced myopic mice in order to study the myopic retina. Additionally, stretched soma and retinas were investigated to simulate myopic conditions. Gap junction blocker-Meclofenamic acid (MFA, 100μM), was applied to the retinas to study the impact of uncoupling AII ACs. Study 1. This study investigated whether the biophysical characteristics of alpha retinal ganglion cells (αRGCs) differ between normal Cx36 knockout mice and those with lens-induced myopia (LIM) retinas. The study applied a generalized linear model (GLM) to predict the coding efficiency between focused and defocused images of RGCs in these mice. Study 2. This study explored whether there are differences in the biophysical responses of alpha retinal ganglion cells (αRGCs) between focused and defocused image stimuli and to observe whether there is a difference in biophysical responses when the soma and retinas were stretched to mimic myopic conditions in both normal and Cx36 KO mice. Study 3 This study investigated whether dopaminergic ACs and AII ACs demonstrated differences in their responses to focused versus defocused images. To uncouple the coupling between AII ACs, gap junction blocker was applied. Study 4. The study investigated whether there are differences in the biophysical responses of horizontal cells (HCs) to focused and defocused images. Summary The neurons in the retina, such as αRGCs, HC, AII ACs, and dopaminergic ACs, can exhibit different responses to focused or defocused images. Gap junctions within retinal circuits might have a significant impact on the development of visually induced myopia. Results Study 1. The study revealed that the intact retinal circuitry, especially connexin 36 (Cx36), is essential in encoding the difference in visual signaling between focused and defocused images. The varied outcomes of the generalized linear model (GLM) with an offset in lens-induced myopia (LIM) retinas indicated the possibility for correction and adaptability within the retinal circuitry of myopic eyes. Study 2. The biophysical response of a single RGC could accurately reflect the image projection of optical stimuli associated with myopic and astigmatic defocus. The process requires an intact retina circuit that includes Cx36. Study 3. Dopaminergic ACs responded with distinctively different biophysical properties to focused and defocused images, thereby potentially influencing dopamine release in the retina and contributing to the development of myopia. Uncoupled AII ACs exhibited the capacity to detect both focused and defocused images, whereas AII ACs with robust coupling possessed the capability to eliminate noise related to defocused images. Study 4. The biophysical properties of HCs allow these cells to reflect spot/annulus pattern stimuli and focused/defocused images. Conclusions This thesis helps to understand the role of Dopaminergic ACs, AII ACs, HCs and Cx36 GJs in decoding and modulating the focused and defocused images, which could be reflected by a single αRGCs. The research may elucidate the neurons in retinal circuit involved in refractive errors and provide potential targets for myopia control. |
| Rights: | All rights reserved |
| Access: | open access |
Copyright Undertaking
As a bona fide Library user, I declare that:
- I will abide by the rules and legal ordinances governing copyright regarding the use of the Database.
- I will use the Database for the purpose of my research or private study only and not for circulation or further reproduction or any other purpose.
- I agree to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage.
By downloading any item(s) listed above, you acknowledge that you have read and understood the copyright undertaking as stated above, and agree to be bound by all of its terms.
Please use this identifier to cite or link to this item:
https://theses.lib.polyu.edu.hk/handle/200/13421