Quantitative approaches to study retinal neurogenesis

The study of the development of the vertebrate retina can be addressed from several perspectives: from a purely qualitative to a more quantitative approach that takes into account its spatio-temporal features, its three-dimensional structure and also the regulation and properties at the systems level. Here, we review the ongoing transition toward a full four-dimensional characterization of the developing vertebrate retina, focusing on the challenges at the experimental, image acquisition, image processing and quantification. Using the developing zebrafish retina, we illustrate how quantitative data extracted from these type of highly dense, three-dimensional tissues depend strongly on the image quality, image processing and algorithms used to segment and quantify. Therefore, we propose that the scientific community that focuses on developmental systems could strongly benefit from a more detailed disclosure of the tools and pipelines used to process and analyze images from biological sample

ANALYSIS OF RETINAL IMAGES FOR GLAUCOMA DIAGNOSIS

Ph.DDOCTOR OF PHILOSOPH

Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo

<p>Abstract</p> <p>Background</p> <p>Teneurins are a unique family of transmembrane proteins conserved from <it>C. elegans </it>and <it>D. melanogaster </it>to mammals. In vertebrates there are four paralogs (teneurin-1 to -4), all of which are expressed prominently in the developing central nervous system.</p> <p>Results</p> <p>Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity.</p> <p>In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.</p> <p>Conclusion</p> <p>Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.</p

The upcoming role of Artificial Intelligence (AI) for retinal and glaucomatous diseases

: In recent years, the role of artificial intelligence (AI) and deep learning (DL) models is attracting increasing global interest in the field of ophthalmology. DL models are considered the current state-of-art among the AI technologies. In fact, DL systems have the capability to recognize, quantify and describe pathological clinical features. Their role is currently being investigated for the early diagnosis and management of several retinal diseases and glaucoma. The application of DL models to fundus photographs, visual fields and optical coherence tomography (OCT) imaging has provided promising results in the early detection of diabetic retinopathy (DR), wet age-related macular degeneration (w-AMD), retinopathy of prematurity (ROP) and glaucoma. In this review we analyze the current evidence of AI applied to these ocular diseases, as well as discuss the possible future developments and potential clinical implications, without neglecting the present limitations and challenges in order to adopt AI and DL models as powerful tools in the everyday routine clinical practice

Small-Molecule Activation of YAP for Inner-Ear Regeneration and Beyond

Hippo signaling is an evolutionarily conserved pathway that restricts organ growth during development and suppresses regeneration in mature organs. Using a highthroughput phenotypic screen, we have identified a potent, non-toxic, and reversible inhibitor of Hippo signaling. An ATP-competitive inhibitor of Lats kinases, the compound causes Yap-dependent proliferation of murine supporting cells in the inner ear, murine cardiomyocytes, and human Müller glia in retinal organoids. The compound promotes the initial stages of the proliferative regeneration of hair cells, a process thought to be permanently suppressed in the adult mammalian inner ear. In conjunction with the Tri- Institutional Therapeutics Discovery Institute, we have thoroughly characterized the compound and generated a suite of over 60 derivatives with improved characteristics such as potency, pharmacokinetics, and specificity. Together, these compounds offer powerful tools for molecular investigations of development, stem cell biology, and regeneration; it is even plausible that drugs related to this novel thiazolimine class will prove useful in therapeutic contexts