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528 results on '"Mohan, Rajiv R."'

30. Keratoconus in Asia

Author

Ghosh, Arkasubhra, Jeyabalan, Nallathambi, Shetty, Rohit, Mohan, Rajiv R., Singh, Arun D., Series editor, Prakash, Gyan, editor, and Iwata, Takeshi, editor

Published
2017
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33. Tissue-targeted and localized AAV5-DCNand AAV5-PEDFcombination gene therapy abrogates corneal fibrosis and concurrent neovascularization in rabbit eyes in vivo

Author

Mohan, Rajiv R., Gupta, Suneel, Kumar, Rajnish, Sinha, Nishant R., Landreneau, James, Sinha, Prashant R., Tandon, Ashish, Chaurasia, Shyam S., and Hesemann, Nathan P.

Abstract

Corneal fibrosis and neovascularization (CNV) after ocular trauma impairs vision. This study tested therapeutic potential of tissue-targeted adeno-associated virus5 (AAV5) mediated decorin (DCN) and pigment epithelium-derived factor (PEDF) combination genes in vivo.

Published
2024
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36. Association of Placental Growth Factor and Angiopoietin in Human Retinal Endothelial Cell-Pericyte co-Cultures and iPSC-Derived Vascular Organoids

Author

Huang, Hu, Saddala, Madhu Sudhana, Mukwaya, Anthony, Mohan, Rajiv R., Lennikov, Anton, Huang, Hu, Saddala, Madhu Sudhana, Mukwaya, Anthony, Mohan, Rajiv R., and Lennikov, Anton

Abstract

PurposePlacental growth factor (PlGF) and Angiopoietin (Ang)-1 are two proteins that are involved in the regulation of endothelial cell (EC) growth and vasculature formation. In the retina and endothelial cells, pericytes are the major source of both molecules. The purpose of this study is to examine the association of PlGF and Ang-1 with human EC/pericyte co-cultures and iPSC-derived vascular organoids.MethodsIn this study, we used co-cultures of human primary retinal endothelial cells (HREC) and primary human retinal pericytes (HRP), western blotting, immunofluorescent analysis, TUNEL staining, LDH-assays, and RNA seq analysis, as well as human-induced pluripotent stem cells (iPSC), derived organoids (VO) to study the association between PlGF and Ang-1.ResultsInhibition of PlGF by PlGF neutralizing antibody in HREC-HRP co-cultures resulted in the increased expression of Ang-1 and Tie-2 in a dose-dependent manner. This upregulation was not observed in HREC and HRP monocultures but only in co-cultures suggesting the association of pericytes and endothelial cells. Furthermore, Vascular endothelial growth factor receptor 1 (VEGFR1) inhibition abolished the Ang-1 and Tie-2 upregulation by PlGF inhibition. The pericyte viability in high-glucose conditions was also reduced by VEGFR1 neutralization. Immunofluorescent analysis showed that Ang-1 and Ang-2 were expressed mainly by perivascular cells in the VO. RNA seq analysis of the RNA isolated from VO in high glucose conditions indicated increased PlGF and Ang-2 expressions in the VO. PlGF inhibition increased the expression of Ang-1 and Tie-2 in VO, increasing the pericyte coverage of the VO microvascular network.ConclusionCombined, these results suggest PlGFs role in the regulation of Ang-1 and Tie-2 expression through VEGFR1. These findings provide new insights into the neovascularization process in diabetic retinopathy and new targets for potential therapeutic intervention.

Published
2023
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37. Corneal Injury Is Associated With Stromal and Vascular Alterations Within Cranial Dura Mater

Author

Glinskii, Olga V., Glinsky, Vladislav V., Xie, Leike, Bunyak, Filiz, Glinskii, Vladimir V., Sinha, Sunilima, Gupta, Suneel, Iozzo, Renato V., Mohan, Rajiv R., Glinskii, Olga V., Glinsky, Vladislav V., Xie, Leike, Bunyak, Filiz, Glinskii, Vladimir V., Sinha, Sunilima, Gupta, Suneel, Iozzo, Renato V., and Mohan, Rajiv R.

Abstract

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as vascular remodeling characterized by alterations in vascular smooth muscle cell (VSMC) morphology, reduced blood vessel VSMC coverage, endothelial cell expression of the fibroblast specific protein 1, and significant increase in the number of podoplanin-positive lymphatic sprouts. Intriguingly, the deficiency of a major extracellular matrix component, small leucine-rich proteoglycan decorin, modifies both the direction and the extent of these changes. As the dura mater is the most important route for the brain metabolic clearance, these results are of clinical relevance and provide a much-needed link explaining the association between ophthalmic conditions and the development of neurodegenerative diseases.

Published
2023

45. Mustard Gas Exposure Actuates SMAD2/3 Signaling to Promote Myofibroblast Generation in the Cornea.

Author

Sinha, Nishant R., Tripathi, Ratnakar, Balne, Praveen K., Suleiman, Laila, Simkins, Katherine, Chaurasia, Shyam S., and Mohan, Rajiv R.

Subjects
CORNEA, CHEMICAL weapons, ALKYLATING agents, OCULAR injuries, OPHTHALMIC drugs, NITROGEN mustards, MUSTARD gas
Abstract

Sulfur mustard gas (SM) is a vesicating and alkylating agent used as a chemical weapon in many mass-casualty incidents since World War I. Ocular injuries were reported in >90% of exposed victims. The mechanisms underlying SM-induced blindness remain elusive. This study tested the hypothesis that SM-induced corneal fibrosis occurs due to the generation of myofibroblasts from resident fibroblasts via the SMAD2/3 signaling pathway in rabbit eyes in vivo and primary human corneal fibroblasts (hCSFs) isolated from donor corneas in vitro. Fifty-four New Zealand White Rabbits were divided into three groups (Naïve, Vehicle, SM-Vapor treated). The SM-Vapor group was exposed to SM at 200 mg-min/m3 for 8 min at the MRI Global facility. Rabbit corneas were collected on day 3, day 7, and day 14 for immunohistochemistry, RNA, and protein lysates. SM caused a significant increase in SMAD2/3, pSMAD, and ɑSMA expression on day 3, day 7, and day 14 in rabbit corneas. For mechanistic studies, hCSFs were treated with nitrogen mustard (NM) or NM + SIS3 (SMAD3-specific inhibitor) and collected at 30 m, 8 h, 24 h, 48 h, and 72 h. NM significantly increased TGFβ, pSMAD3, and SMAD2/3 levels. On the contrary, inhibition of SMAD2/3 signaling by SIS3 treatment significantly reduced SMAD2/3, pSMAD3, and ɑSMA expression in hCSFs. We conclude that SMAD2/3 signaling appears to play a vital role in myofibroblast formation in the cornea following mustard gas exposure. [ABSTRACT FROM AUTHOR]

Published
2023
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46. Corneal Regeneration Using Gene Therapy Approaches.

Author

Sarkar, Subhradeep, Panikker, Priyalakshmi, D'Souza, Sharon, Shetty, Rohit, Mohan, Rajiv R., and Ghosh, Arkasubhra

Subjects
GENE therapy, CORNEA, SURGICAL complications, CORNEAL transplantation, GRAFT rejection
Abstract

One of the most remarkable advancements in medical treatments of corneal diseases in recent decades has been corneal transplantation. However, corneal transplants, including lamellar strategies, have their own set of challenges, such as graft rejection, delayed graft failure, shortage of donor corneas, repeated treatments, and post-surgical complications. Corneal defects and diseases are one of the leading causes of blindness globally; therefore, there is a need for gene-based interventions that may mitigate some of these challenges and help reduce the burden of blindness. Corneas being immune-advantaged, uniquely avascular, and transparent is ideal for gene therapy approaches. Well-established corneal surgical techniques as well as their ease of accessibility for examination and manipulation makes corneas suitable for in vivo and ex vivo gene therapy. In this review, we focus on the most recent advances in the area of corneal regeneration using gene therapy and on the strategies involved in the development of such therapies. We also discuss the challenges and potential of gene therapy for the treatment of corneal diseases. Additionally, we discuss the translational aspects of gene therapy, including different types of vectors, particularly focusing on recombinant AAV that may help advance targeted therapeutics for corneal defects and diseases. [ABSTRACT FROM AUTHOR]

Published
2023
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