INTRODUCTION: As populations are adopting a Western lifestyle, with high intake of dietary sugar and fat and low physical activity, the risk of developing Type 2 Diabetes is only increasing dramatically. Diabetes leads to drastic alterations within the body, primarily leading to neuropathies, nephropathies and retinopathies. As the prevalence of diabetes increases, it is important to understand the threat that it poses to the retina, and ultimately, vision. OBJECTIVE: We plan to compare the retina of diabetic patients with retinopathies to normal, healthy patients to understand the differences between them. We will be using a novel imaging technique, called Laser Speckle Flowgraphy, which provides the Mean Blur Rate, a value directly related to the blood flow velocity within the retina, specifically the optic nerve head. Using the calculated Mean Blur Rate, this study will quantify baseline blood flows in patients with diabetic retinopathies. This project aims to understand and differentiate the Mean Blur Rate of healthy patients and diabetic patients, including inter-patient and intra-patient comparisons, as well as changes in the Mean Blur Rate over time. The potential influence of treatment factors, such as intravitreal injection treatment or laser treatment, or demographic factors, such as age and race, on the Mean Blur Rate of diabetic retinopathy patients will also be evaluated. By understanding the difference in the retinas of diabetic patients and healthy patients, we can work towards preventing the loss of vision and function. METHODS: A total of 25 Type 2 diabetic patients with a diabetic retinopathy equaling 46 eyes were compared to 20 healthy patients, equaling 40 eyes. We collected the Mean Blur Rate for comparison between the two populations. Data was compared with correlation, t-test and ANOVA studies to find whether demographic or treatment variables influenced the Mean Blur Rate of diabetic retinopathy patients. RESULTS: We found a difference between the Mean Blur Rate, and thus blood flow, between the retina of diabetic and healthy patients. Diabetic patients tended to have a lower flow, presumably attributable the effects of hyperglycemia on blood circulation. Diabetic patients also have a significant difference in the Mean Blur Rate between both of their eyes, indicating that their hyperglycemia may affect both eyes differently (p<0). There was significant variability within both diabetic retinopathy patients and normal, healthy patients (p<0 for healthy patients and p<0.001 for diabetic patients). This is expected as blood circulation can be affected by a variety of factors other than disease status. We also found that the MBR of diabetics who were treated with intravitreal injections was on average higher than those who had not received intravitreal treatment. (p<0.05) CONCLUSION: Our study highlights how diabetic retinopathy impacts retinal blood flow, as well as showcases how Laser Speckle Flowgraphy can be used as a reliable method to measure and compare retinal blood velocities. Further studies are needed to understand how exactly diabetes affects blood circulation, although several theories are currently available. We also found a relation between previous intravitreal injection history and the blood flow velocity, but other studies have had mixed results on how exactly these injections alter the blood flow within the retina. Future studies can be conducted to better understand this relationship and uncover whether the effect on blood flow velocity is related to the drug used for the intravitreal injection or some other factor.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第21610号 / 理博第4517号 / 新制||理||1648(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)准教授 今元 泰, 教授 高田 彰二, 教授 杤尾 豪人 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22004号 / 医博第4518号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 辻川 明孝, 教授 中川 一路, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18864号 / 医博第3975号 / 新制||医||1008(附属図書館) / 31815 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 坂田 隆造, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

PURPOSE: Normobaric hyperoxia (NBH) has been shown in animal models of experimental retinal detachment (RD) to effectively prevent photoreceptor degeneration. Furthermore, choroidal hyperpermeability has been implicated in the disease pathophysiology. In this study, we studied the effects of 3-hours of 40% FIO2 NBH on photoreceptor morphology and visual acuity in patients with vision loss associated with active central serous chorioretinopathy (CSCR). MATERIALS and METHODS: A total of 8 patients with active unilateral CSCR received at least one 3-hour NBH (40% FIO2) session. Best corrected visual acuity (BCVA) as well as thickness of the central macula, subretinal fluid (SRF), photoreceptor layer (PL), and outer nuclear layer (ONL) were assessed. RESULTS: In patients with unilateral acute CSCR, 3 hours of 40% FIO2 NBH showed a trend towards improved vision, but no statistical differences were obtained for BCVA, CMT, SRF, PL, or ONL. CONCLUSIONS: Administration of 3-hours of NBH did not induce any measurable anatomic changes in the retina nor any significant changes in visual acuity. These results challenge the hypothesis of choroidal hyperpermeability in CSCR and suggest that additional or alternative pathologies contribute to this disease. / 2022-11-29T00:00:00Z

Indiana University-Purdue University Indianapolis (IUPUI) / Hydrocephalus affects 1 in 1,000 newborns and nearly 1,000,000 Americans, leading to an increase in intercranial pressure due to the build-up of cerebrospinal fluid. There are numerous complications that arise as a result of hydrocephalus, but this study focuses on optic disc edema. The subarachnoid space surrounding the optic nerve contains cerebrospinal fluid. The cerebrospinal fluid increases in hydrocephalus, putting pressure on the optic nerve. The additional intracranial pressure has been proposed to cause axoplasmic stasis within the retinal ganglion cell axons, leading to axonal damage and retinal ischemia. The purpose of this study was to determine the effects of hydrocephalus on the optic disc and retina in several animal models of hydrocephalus. This study uses two genetic and two injury-induced models of hydrocephalus in addition to immunohistochemistry and histological stains to examine the optic disc, thickness of retinal layers, and numbers of retinal cells. This study serves as preliminary work to help build the case that hydrocephalus causes cell loss in the retina, as well as swelling of the retinal ganglion cell axons, leading to axoplasmic stasis and cell death. / Indefinitely

Magister Public Health - MPH / Untreated and unmonitored diabetic retinopathy (DR) can lead to vision loss. This may have many negative implications on society. Currently, there is a dearth of evidence regarding the factors that influence compliance behaviour to treatment among patients diagnosed with DR in South Africa’s public healthcare system. The current study sought to fill this research gap and explore patient-, institution-, treatment-, and COVID-19- related factors associated with compliance behaviour among patients living with diabetes that have been referred for suspected vision-threatening DR in the Northern/Tygerberg sub-structure (NTSS) of Cape Town, South Africa. Methodology: A qualitative research approach was used. The study population included 19 years and older South Africans living with diabetes who were screened and referred for vision-threatening retinopathy within the last 18 months at public primary healthcare facilities in the NTSS.

No description available.

Melatonin is an indolamine hormone presumably synthesized by retinal photoreceptors, and may act as a paracrine signal of darkness within the retina. Previous studies have suggested that melatonin, acting through specific receptors, may be involved in cyclic retinal functions such as photoreceptor outer segment disc shedding and phagocytosis, and modulation of neurotransmitter release in the inner retina. The goal of this study was to determine if melatonin receptor mRNA is expressed in the neural retina and retinal pigment epithelium (RPE) of Xenopus laevis. Sheets of RPE, devoid of contaminating cells, were obtained from Xenopus eyes, and epithelial cultures were subsequently established on microporous membrane filters in a defined medium. Total RNA was isolated from whole brain, neural retina, fresh RPE sheets, and cultured RPE cells. RNA expression of the three known Xenopus melatonin receptor subtypes (MEL1A, 1B, and 1C) was determined by reverse- transcription/polymerase chain reaction (RT/PCR) amplification, followed by Southern hybridization with RNA probes. PCR-amplified cDNA encoding melatonin receptor subtypes 1B and 1C, but not 1A, were detected in reverse-transcribed RNA obtained from brain, neural retina and RPE. RPE cells grown in culture for two weeks also demonstrated 1B and 1C receptor RNA expression. This study suggests that RNA encoding the 1B and 1C melatonin receptor subtypes is expressed in the neural retina and RPE of Xenopus retina, and the expression persists in RPE cells when grown in culture. The expression of melatonin receptor RNA in the RPE may reflect a regulatory role for melatonin in some diurnal events that occur in this tissue, such as phagocytosis of photoreceptor outer segment membranes, and intracellular migration of pigment granules.

Indiana University-Purdue University Indianapolis (IUPUI) / Retinal ganglion cells (RGCs) serve as a vital connection between the eye and the brain with damage to their axons resulting in loss of vision and/or blindness. Reti- nal organoids are three-dimensional structures derived from human pluripotent stem cells (hPSCs) which recapitulate the spatial and temporal differentiation of the retina, providing a valuable model of RGC development in vitro. The working hypothesis of these studies is that hPSC-derived RGCs are capable of extensive outgrowth and display target specificity and pathfinding abilities. Initial efforts focused on charac- terizing RGC differentiation throughout early stages of organoid development, with a clearly defined RGC layer developing in a temporally-appropriate manner express- ing a compliment of RGC-associated markers. Beyond studies of RGC development, retinal organoids may also prove useful to investigate and model the extensive axonal outgrowth necessary to reach post-synaptic targets. As such, additional efforts aimed to elucidate factors promoting axonal outgrowth. Results demonstrated significant enhancement of axonal outgrowth through modulation of both substrate composi- tion and growth factor signaling. Furthermore, RGCs possessed guidance receptors that are essential in influencing outgrowth and pathfinding. Subsequently, to de- termine target specificity, aggregates of hPSC-derived RGCs were co-cultured with explants of mouse lateral geniculate nucleus (LGN), the primary post-synaptic target of RGCs. Axonal outgrowth was enhanced in the presence of LGN, and RGCs dis- played recognition of appropriate targets, with the longest neurites projecting towards LGN explants compared to control explants or RGCs grown alone. Generated from xvii the fusion of regionally-patterned organoids, assembloids model projections between distinct regions of the nervous system. Therefore, final efforts of these studies focused upon the generation of retinocortical assembloids in order to model the long-distance outgrowth characteristic of RGCs. RGCs displayed extensive axonal outgrowth into cortical organoids, with the ability to respond to environmental cues. Collectively, these results establish retinal organoids as a valuable tool for studies of RGC develop- ment, and demonstrate the utility of organoid-derived RGCs as an effective platform to study factors influencing outgrowth as well as modeling long-distance projections and pathfinding abilities.