Browsing by Author "Belamkar, Ameya"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Characterization of the Ocular Phenotype in a Col4a3 Knockout Mouse Model of Alport Syndrome
    (Association for Research in Vision and Ophthalmology, 2024) Belamkar, Ameya; Luo, Qianyi; Mahajan, Neha; Abhyankar, Surabhi; Jones, Bryce A.; Sodhi, Rupinder Kaur; Pattabiraman, Padmanabhan P.; Levi, Moshe; Bhatwadekar, Ashay D.; Ophthalmology, School of Medicine
    Purpose: Alport syndrome (AS) is a genetic condition caused by a dysfunctional collagen (IV) α3α4α5 heterotrimer, leading to basement membrane instability and, ultimately, abnormalities in the kidney, inner ear, and eyes. This study aimed to characterize ocular pathology of AS by focusing on inflammatory and fibrotic markers. Methods: Col4a3tm1Dec knockout (KO) mice eyes were evaluated for the localization of collagen (IV) α3 and collagen (IV) α4, then stained for transforming growth factor-β1 (TGF-β1), TGF-β2, connective tissue growth factor (CTGF), and β-catenin. mRNA levels of the profibrotic genes S100a4, Acta2, Col1a1, Snai1, Snai2, and Twist1 were assessed using real-time reverse transcription quantitative PCR (RT-qPCR). Results: Collagen (IV) α3 and collagen (IV) α4 were co-expressed in Descemet's and Bruch's membrane but not in the retina, lens, or other corneal substructures. Immunofluorescence quantitation revealed upregulation of TGF-β1 in the anterior lens and TGF-β2 in the retina of KO eyes. Conversely, CTGF and β-catenin were shown to be elevated in the corneal epithelium but not the retina or lens. RT-qPCR showed an increase in the transcription of Acta2, Col1a1, and Snai2 in the retinas and Snai2 in anterior segments of KO mice. Conclusions: Col4a3 KO mice exhibited a differential inflammatory and profibrotic response in the cornea, retina, and lens, which may play a role in the ocular pathology of AS.
  • Thumbnail Image
    Item
    Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World
    (MDPI, 2021-07-31) Bhatwadekar, Ashay D.; Shughoury, Aumer; Belamkar, Ameya; Ciulla, Thomas A.; Ophthalmology, School of Medicine
    Diabetic retinopathy (DR) is a chronic complication of diabetes and a leading cause of blindness in the industrialized world. Traditional risk factors, such as glycemic control and duration of diabetes, are unable to explain why some individuals remain protected while others progress to a more severe form of the disease. Differences are also observed in DR heritability as well as the response to anti-vascular endothelial growth factor (VEGF) treatment. This review discusses various aspects of genetics in DR to shed light on DR pathogenesis and treatment. First, we discuss the global burden of DR followed by a discussion on disease pathogenesis as well as the role genetics plays in the prevalence and progression of DR. Subsequently, we provide a review of studies related to DR's genetic contribution, such as candidate gene studies, linkage studies, and genome-wide association studies (GWAS) as well as other clinical and meta-analysis studies that have identified putative candidate genes. With the advent of newer cutting-edge technologies, identifying the genetic components in DR has played an important role in understanding DR incidence, progression, and response to treatment, thereby developing newer therapeutic targets and therapies.