An Immunohistochemical Study of Retinal Collagen IV Expression during Pre- and Postnatal Postnatal Periods in Balb/c Mice

Objective: Basement membranes are specialized extracellular matrices which playimportant roles such as cell regulation, proliferation and migration. Collagen fibers,especially type IV, are the most important basement membrane constituents. As retinais one of the target organs in diabetes mellitus, and nephropathy is a major cause ofend stage renal and retinal diseases resulting in increased morbidity and mortality,early diagnosis leads to better treatment. Hence, in this investigation, the appearanceand distribution of collagen IV during gestational days and early postnatal periodswere observed.Materials and Methods: 24 intact female Balb/c mice were kept under normal conditions.After mating, appearance of a vaginal plug was assumed as day zero of the pregnancy.From days 13-18 of gestation, the pregnant mice were euthanised and theirembryos as well as pups from days 1 to 5 were collected. For histochemichal studies,heads of the specimens were fixed, serially sectioned and immunohistochemicallstudies were performed by using monoclonal antibodies for tracing of collagentype IV.Results: Our findings revealed that the amount of collagen IV in the internal limiting membrane(ILM) and extra cellular matrix (ECM) of the retina, as well as vessels of the vitreusbody appear on embryonic day 16. Also, a patchy distribution was observed in the pigmentedepithelium which continued to further develop until the end stage of embryoniclife. Strong labeling was observed until postnatal day 3 but did not increase significantlythereafter.Conclusion: These findings establish the importance of collagen IV during the critical periodof retinal development. In addition, this study indicates that high levels of collagen IVare present in the basal membrane (BM) of the inner limiting membranes and pigmentedepithelium (3rd post natal on the 3rd postnatal day

The Role of Type IV Collagen in Developing Lens in Mouse Fetuses

Objective(s)Extracellular matrix (ECM) and basement membrane (BM) play important roles in many developmental processes during development and after birth. Among the components of the BM, collagen fibers specially type IV are the most important parts. The aim of this study was to determine the time when collagen type IV appears in the BM of lens structure during mouse embryonic development.Materials and MethodsIn this experimental study, 22 female Balb/C mice were randomly selected and were kept under normal condition, finding vaginal plug was assumed as day zero of pregnancy. From embryonic day 10 to 20, all specimens were sacrificed by cervical dislocation and their heads were fixed, serially sectioned and immunohistochemistry study for tracing collagen type IV in lens were carried out.ResultsOur data revealed that collagen type IV appeared at the early stage of gestation day 12 in BM of anterior epithelial lens cells and the amount of this protein gradually increased until days 15-17 in ECM and posterior capsule epithelium. After this period, severe reaction was not observed in any part of the lens.ConclusionThese findings establish the important role of collagen IV in developing optic cup and any changes during critical period of pregnancy may be result in severe visual system defec

Ultra-Large-Scale Screening of Natural Compounds and Free Energy Calculations Revealed Potential Inhibitors for the Receptor-Binding Domain (RBD) of SARS-CoV-2

The emergence of immune-evading variants of SARS-CoV-2 further aggravated the ongoing pandemic. Despite the deployments of various vaccines, the acquired mutations are capable of escaping both natural and vaccine-induced immune responses. Therefore, further investigation is needed to design a decisive pharmacological treatment that could efficiently block the entry of this virus into cells. Hence, the current study used structure-based methods to target the RBD of the recombinant variant (Deltacron) of SARS-CoV-2, which was used as a model variant. From the virtual drug screenings of various databases, a total of four hits were identified as potential lead molecules. Key residues were blocked by these molecules with favorable structural dynamic features. The binding free energies further validated the potentials of these molecules. The TBE for MNP was calculated to be −32.86 ± 0.10 kcal/mol, for SANC00222 the TBE was −23.41 ± 0.15 kcal/mol, for Liriodenine the TBE was −34.29 ± 0.07 kcal/mol, while for Carviolin the TBE was calculated to be −27.67 ± 0.12 kcal/mol. Moreover, each complex demonstrated distinct internal motion and a free energy profile, indicating a different strategy for the interaction with and inhibition of the RBD. In conclusion, the current study demands further in vivo and in vitro validation for the possible usage of these compounds as potential drugs against SARS-CoV-2 and its variants