Biology subjects

Pandala, N.

Publications and source records attributed to Pandala, N..

4 recordsLinked to original sources

bioRxiv2025

Acriflavine delivery via Polyurethane nanocapsules to treat neovascular age-related macular degeneration

Choroidal neovascularization is a complication associated with retinal diseases such as age-related macular degeneration (AMD), a leading cause of vision loss in the developed world. Choroidal neovascular membrane (CNVM) refers to the abnormal growth of blood vessels in the retina which results in exudation and/or hemorrhage, leading to photoreceptor damage and vision loss. Currently first-line treatment for CNVM include intravitreal injections of vascular endothelial growth factor (VEGF)-binding antibodies that prevent the growth of these leaky blood vessels. Unfortunately, anti-VEGF drugs often require frequent injections, and prolonged VEGF inhibition has been associated with retinal atrophy and decreased long term effectiveness in some patients. This study presents the use of Acriflavine, a small molecule HIF1 inhibitor loaded polyurethane nanocapsules to treat CNVM in a rat model. Fourteen days following laser injury and intravitreal drug administration, CMVM size was significantly reduced in acriflavine nanocapsule and free acriflavine treated animals as compared to drug free controls. Moreover, acriflavine nanocapsules reduce CNVM incidence compared to drug free controls by approximately 25%. Among the different delivery routes tested, intravitreal delivery of acriflavine nanocapsules was found to be superior to subretinal and suprachoroidal delivery for reducing CNVM area without causing significant damage to the neural retina. This paper presents the synthesis, characterization and the effectiveness of the polyurethane based acriflavine delivery system in treating choroidal neovascularization.

pharmacology and toxicology↗

bioRxiv2025

Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement

PurposeChoroidal loss is an important pathophysiological step in many retinal diseases, but few reliable translational models of choroidal injury exist. Here, we report a new targeted choroidal injury model using bioconjugated saporins and compare it models of systemic sodium iodate administration. MethodsWild-type Sprague-Dawley rats were given suprachoroidal injections of anti-CD38 or anti-CD105 antibodies conjugated to saporin immunotoxin (10 {micro}l at 0.05 {micro}g/{micro}L) to induce selective choroidal endothelial cell injury. These animals were compared to wild-type rats given sodium iodate (75 mg/kg) via tail vein injections, with a dose escalation study (25, 50, and 75 mg/kg) in immunocompromised (Sprague-Dawley Rag2/Il2g double-knockout) rats. Animals were examined at 1-, 2-, and 3-weeks post-treatment, and the degree of choroidal injury compared using fundus photography, optical coherence tomography, and immunohistochemistry. ResultsSuprachoroidal administration of anti-CD38 or anti-CD105 saporins resulted in severe choroidal vascular injury localized to the injection site, without damage to adjacent choroidal vasculature, progressive injury over time, or development of choroidal neovascularization. By contrast, sodium iodate treated animals had rapid, diffuse choroidal loss which progressed throughout the study time points, with fatal systemic side effects at the highest (75 mg/kg) dose. ConclusionsSuprachoroidal injection of anti-CD38 and anti-CD105 saporins results in targeted, localized, non-progressive choroidal injury in rats. These models offer alternatives to systemic sodium iodate administration, which causes diffuse, progressive choroidal injury. Translational RelevanceImmunotoxin-based models of targeted choroidal injury may be useful for understanding pathways of retinal degeneration and facilitating development of therapies for diseases involving choroidal cell loss.

neuroscience↗

bioRxiv2025

Novel Protein Structure Validation using PDBMine and Data Analytics Approaches

Protein structure prediction is essential for understanding biological functions and advancing drug development. Although experimental techniques like NMR, X-ray crystallography, and cryo-EM provide valuable insights, they are expensive and time-consuming, prompting reliance on computational approaches. AlphaFold2 revolutionized protein model predictions accuracy in 2020. However, limitations remain in the prediction of novel proteins, complex conformations, and mutations. To address these challenges, we leverage PDBMine software and machine learning for advanced data analytics. This approach detects and corrects structural inaccuracies, calculates fitness scores, and enhances model reliability, accelerating drug discovery and therapeutic breakthroughs by bridging gaps in current protein prediction capabilities.

bioinformatics↗

bioRxiv2024

Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration

In retinal diseases such as age-related macular degeneration (AMD) and choroideremia, a key pathophysiologic step is loss of endothelial cells of the choriocapillaris, the dense vascular bed required for maintaining health and function of the retina. As such, repopulation of choroidal vasculature early in the disease process may halt disease progression. Prior studies have shown that injection of donor cells in suspension results in significant cellular efflux and poor cell survival. As such, the goal of this study was to develop a hydrogel system designed to support CEC transplantation. A library of hydrogels was synthesized using laminin (i.e., LN111, LN121, and LN421), carboxy methyl chitosan, and oxidized dextran via reversible Schiff base chemistry. Each of the developed hydrogels was readily injectable into the suprachoroidal space, with excellent gelation, mechanical, and degradation properties. Laminin-based hydrogels were compatible with immortalized CEC survival in vitro, and suprachoroidal injection of LN111 and LN121 containing gels were well-tolerated in an in vivo rat model, whereas LN421 containing gels caused significant chorioretinal inflammation. Hydrogels were detected in the suprachoroidal space of immunosuppressed rats at 1-week post-injection and were completely resorbed by 1-month post-injection. There were significantly more CECs retained in immunosuppressed rats that received cell laden hydrogels than those that received unsupported cell suspensions (i.e., CECs only). These findings pave the way for future CEC replacement studies in animal models of choroidal cell loss toward the development of future therapies. Statement of significanceAge related macular degeneration (AMD) is a leading cause of untreatable blindness in the industrial world. A key pathologic step in AMD is loss of the choriocapillaris endothelial cells, which provide vascular support to the overlying retina, including the light-sensing photoreceptors. We believe that choroidal cell replacement early in disease may prevent retinal cell death and subsequent vision loss. In this study, we present a strategy for repopulating the choriocapillaris using choroidal endothelial cell laden hydrogels. Specifically, we demonstrate the synthesis and characterization of 3 different laminin-based hydrogel systems. LN111 and LN121 hydrogels were found to increase retention of choroidal endothelial cells following suprachoroidal transplantation. These findings pave the way for future cell replacement studies in animal models of choroidal cell dropout.

bioengineering↗