Diabetic retinopathy (DR) was characterized by numerous hyperglycemia-dependent cellular and pathological changes in the retina, including retinal ischemia/reperfusion (I/R) injury. To determine the role of the 2nd enzyme of polyol pathway in relation with the pathogenesis in ischemic retinopathy, SDH deficient mice, C57BL/LiA, that lacked SDH activity, was used to study the pathogenesis of diabetic retinopathy, which also included I/R injury. Wild type and SDH-deficient mice were subjected to I/R injury by transiently occluding middle cerebral artery for two hours and twenty-two hour of reperfusion. The rationale of this study was to investigate the effect by blocking the conversion of sorbitol to fructose by SDH null mutation (SDH -/-), leading to accumulation of sorbitol level and reduction of oxidative stress, as demonstrated by the polyol pathway. Results: After induction with transient MCAO, there was increase in the thickness of OLM to ILM ipsilateral SDH+/+ compared with contralateral SDH+/+ (from 84 +/- 1 to 96 +/- 2 μm) while that of ipsilateral SDH-/- compared with contralateral SDH -/- (from 77 +/- 2 to 90 +/- 2 μm) suggested that there was edema after ischemic reperfusion injury. The result showed that there was increased cellular edema in ipsilateral retina of both SDH +/+ and SDH -/- retina after transient MCAO. The level of immunoreactivity against Aquaporin-4 and nitrotyrosine in studying the presence of oxidative stress; glutamine synthetase and glutamate in studying the toxicity of astrocyte glutamate; sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in studying the regulation Ca2+ homeostasis was determined using immunohistochemistry. For all the antibodies, there was similar immunoreactivity level between the contralateral side of both SDH+/+ and SDH -/- mice. For the SDH+/+ group, there was increase in signal in the ipsilateral retina in comparison with the contralateral one. On the other hand, for the SDH-/- group, similar result was observed. There was increase in signal and it was found more in the ipsilateral retina in comparison with the contralateral retina. Finally, in the ipsilateral retina of both SDH +/+ and SDH -/- mice, increased immunoreactivity was found in both but their difference was not statistically significant. This concluded that SDH deletion and subsequent accumulation of sorbitol metabolites did not contribute significantly in the role of pathogenesis of ischemic retinopathy especially in mice after I/R injury. / published_or_final_version / Anatomy / Master / Master of Medical Sciences

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Includes bibliographical references.

Thesis (Ph.D.)--Baylor University, 2006. / Includes bibliographical references (p. 88-90).

The accurate assessment of human diabetic somatic polyneuropathy (DSPN) is important to define at risk patients, predict deterioration, and assess the efficacy of pathogenetic treatments. Corneal confocal microscopy (CCM) has been proposed as a surrogate endpoint for DSPN. Approximately 50% of patients with DSPN experience neuropathic pain or symptoms and the underlying reasons are not clearly elucidated. Vitamin D deficiency has been associated with diabetic complications including DSPN and diabetic retinopathy (DR). However there is a paucity of data regarding the interaction of vitamin D status with diabetic complications. This thesis shows that CCM can readily detect small fibre neuropathy prior to large fibre involvement and assess rapidly progressive nerve fibre loss prior to conventional thermal threshold testing. CCM has a superior diagnostic capabilities compared to intra-epidermal nerve fibres and correlates better with nerve conduction studies. Patients with LADA have a greater prevalence of small fibre neuropathy compared to matched patients with type 2 diabetes. Vitamin D deficiency is highly prevalent in patients with diabetes and despite relatively aggressive replacement regimens are inadequate in raising vitamin D levels in a significant proportion of patients. Vitamin D deficiency is not associated with DR but there is a strong association between painful DSPN and vitamin D insufficiency and more so with overt deficiency.

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.

PURPOSE: Ischemic retinopathies such as diabetic retinopathy (DR), retinal vein occlusions (RVO), and age-related macular degeneration (AMD) are ocular diseases caused by abnormal changes in the microvasculature that results in ischemia. This is often followed by a secondary phase characterized by pathological neovascularization and leakage of fluid, which contributes to a loss of visual acuity in affected patients. Anti-VEGF therapy, the current standard of treatment for ischemic retinopathies, is invasive, costly, and lacks a known treatment period. Supplemental oxygen provides the therapeutic potential of not only oxygenating hypoxic retinal cells, but also reducing the neovascularization and edema associated with many ischemic retinopathies through the downregulation of proangiogenic and pro-inflammatory cytokines.The objective of this study is to understand the biochemical underpinnings of treating ischemic retinopathies with hyperoxia. The elucidation of the effect hyperoxia on the molecular level may help guide the development of future studies regarding this novel treatment. METHODS: 68 undiluted vitreous samples were obtained during pars plana vitrectomy (PPV) and the concentration analysis of 34 proteins was analyzed using the Bio-Plex Pro Human Cancer Biomarker Assay. Vitreous samples were divided into three groups: (1) eyes of patients who underwent PPV for epiretinal membrane peeling (ERMP) and/or macular hole (MH) with no history of diabetes mellitus (non-DM group); (2) eyes of patients who underwent PPV for ERMP and/or MH with a history of diabetes or nonproliferative diabetic retinopathy (DM group); (3) eyes of patients who underwent PPV for proliferative diabetic retinopathy (PDR group). Mann-Whitney U tests were performed to compare the biomarker concentrations between the three groups. RESULTS: Numerous growth factors and inflammatory cytokines were significantly upregulated between the non-DM and PDR groups - Angiopoietin-2, EGF, Endoglin, G-CSF, HB-EGF, HGF, PDGF, PIGF, sHER2/neu, TIE-2, VEGF-A, VEGF-D, IL-18, IL-6, IL-8, PECAM-1, sCD40L, SCF, sFASL, sIL-6Ra, TNF-⍺, Leptin, PAI-1, and uPA. A literature search of these proteins revealed many to be directly activated by HIF-1 transcription factor, which is the "master switch" for genes transcribed during a hypoxic event. CONCLUSION: The abundance of proangiogenic and pro-inflammatory factors in PDR that are also upregulated by HIF-1 demonstrate the potential for using hypoxia to treat PDR (and other ischemic retinopathies) through the reduction of HIF-1. This study also shows the wide variability in the expression levels of these proteins which helps provide a better understanding of their degree of involvement in the pathogenesis of ischemic retinopathies. / 2021-06-14T00:00:00Z

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第21266号 / 社医博第89号 / 新制||社医||10(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 辻川 明孝, 教授 中山 健夫, 教授 小杉 眞司 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

The Temple University Hospital System Ophthalmology Department implemented a telemedicine screening program for diabetic retinopathy to improve patient care and community engagement. The program screened over 1900 patients in the Philadelphia area from March 2016 to March 2020 and identified a significant number of patients who required further in-person examination and treatment. The implementation of a telemedicine screening program for diabetic retinopathy raises important ethical issues and merits discussion of the impact of social determinants of health on healthcare outcomes. In these community initiatives, the principles of agency, beneficence, non-maleficence, social justice, and solidarity in bioethics should be considered as they pertain to the specific needs of the community in which they are implemented. Overall, the COVID-19 pandemic has highlighted the importance of considering the ethical implications of healthcare practices, including diabetic retinopathy screenings. The risks and barriers to access must be taken into account, especially for vulnerable populations in urban areas. As such, promoting primary care engagement, providing accurate and culturally appropriate education and outreach, and addressing social determinants of health can help ensure that all patients have access to comprehensive and equitable care. By considering these factors, diabetic retinopathy screenings can be conducted in an ethical and effective manner. / Urban Bioethics

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24498号 / 医博第4940号 / 新制||医||1064(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 中本 裕士, 教授 森本 尚樹, 教授 大森 孝一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM