Taneja College of Pharmacy

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Biswal Lab

Research

Biswal Lab Research

 
Retinal degeneration control

Studying mechanism of oxidative stress induced changes in Retinal Pigment Epithelium (RPE) that controls retinal degeneration

Age-related macular degeneration (AMD) causes vision loss among many older individuals, and the retinal pigment epithelium (RPE) is thought to be a critical site of injury. Vision loss in AMD occurs due to photoreceptor degeneration and/or choroidal neovascularization. Geographic atrophy (GA), the advanced form of dry AMD, is characterized by the breakdown of RPE, choriocapillaris, and photoreceptors, especially in the macula. Lack of clear understanding of the molecular mechanisms of GA hinders the development of therapy. For lifelong maintenance of photoreceptors, RPE cells play an essential role in phagocytosis and degradation of tips shed from photoreceptor outer segments (POS). Photoreceptors and RPE cells are susceptible to injury from mitochondrial oxidative stress. The central goal of the project is to understand how photoreceptor degeneration occurs in GA. We hypothesize that oxidative stress impairs phagocytosis and lysosome function and ultimately activates inflammatory processes in RPE that stimulate geographic atrophy. We are testing our hypothesis in RPE cell culture and in a new mouse model of age-dependent RPE atrophy.
Laser induced CNV by fungus imaging, RPE flat mount& OCT

Developing and testing potential translational therapy (Gene/Drug/Nano) for treating retinal degenerative and vascular diseases

The abnormal growth of blood vessels in the eye may originate from cornea, retina and choroid. New blood vessels originating from the choroid layer is a major implication in wet age-related macular degeneration (wet-AMD). New blood vessels originating from retina are the clinical phenotype for diabetic retinopathy (DR) and retinopathy of prematurity (ROP). In either case, local secretion of VEGF induces uncontrolled neovascularization that ultimately causes irreversible damage to the retina causing a loss of vision that cannot be restored. Retinal degeneration is associated with loss of photoreceptor cells and RPE that is caused due to prolonged oxidative stress. We are testing different potential AAV mediated therapeutic genes that can be used to protect retinal cells and RPE. We are also testing different FDA approved drugs and new drugs that have the capacity to prevent retinal degeneration and abnormal neovascularization. Students from MSPN graduate program focus on developing and testing different nanoparticle based approach that carry genes and drugs to protect the retina from oxidative and inflammatory insult. We are using different model systems to test novel translational therapy that will be useful to treat retinal degenerative and vascular diseases.

Publications

  • 029. Biswal MR*, Wang Z, Paulson RJ, Uddin RR, Tong Y, Zhu P, Li H, Lewin AS. Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium. Antioxidants. 2021; 10(6):842. https://doi.org/10.3390/antiox10060842. (*Corresponding author).

    028. Solanki AK, Biswal MR, Walterhouse S, Martin R, Kondkar AA, Knölker H-J, Rahman B, Arif E, Husain S, Montezuma SR, Nihalani D, Lobo GP. Loss of Motor Protein MYO1C Causes Rhodopsin Mislocalization and Results in Impaired Visual Function. Cells. 2021; 10(6):1322. https://doi.org/10.3390/cells10061322

    027. Rohrer B, Biswal MR, Obert E, Dang Y, Su Y, Zuo X, Fogelgren B, Kondkar AA, Lobo GP, Lipschutz JH. Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function. International Journal of Molecular Sciences. 2021; 22(10):5083. https://doi.org/10.3390/ijms22105083

    026. Biswal MR*, Bhatia S. Carbon Dot Nanoparticles: Exploring the Potential Use for Gene Delivery in Ophthalmic Diseases. Nanomaterials (Basel). 2021 Apr 6;11(4):935. doi: 10.3390/nano11040935. PMCID: PMC8067473. (*Corresponding author)

    025. Lobo GP, Biswal MR, Kondkar AA. Editorial: Molecular Mechanisms of Retinal Cell Degeneration and Regeneration. Front Cell Dev Biol. 2021 Mar 5;9:667028. doi: 10.3389/fcell.2021.667028. PMID: 33748148; PMCID: PMC7973204.

    024. Khiev D, Mohamed ZA, Vichare R, Paulson R, Bhatia S, Mohapatra S, Lobo GP, Valapala M, Kerur N, Passaglia CL, Mohapatra SS, Biswal MR*. Emerging Nano-Formulations and Nanomedicines Applications for Ocular Drug Delivery. Nanomaterials (Basel). 2021 Jan 12;11(1):E173. doi: 10.3390/nano11010173. PMID: 33445545. (*Corresponding author)

  • 023. Garner I, Vichare R, Paulson R, Appavu R, Panguluri SK, Tzekov R, Sahiner N, Ayyala R, Biswal MR*. Carbon Dots Fabrication: Ocular Imaging and Therapeutic Potential. Front Bioeng Biotechnol. 2020 Sep 25;8:573407. doi: 10.3389/fbioe.2020.573407. PMID: 33102456; PMCID: PMC7546398. (*Corresponding author)

    022. Mohapatra, S.S.; Frisina, R.D.; Mohapatra, S.; Sneed, K.B.; Markoutsa, E.; Wang, T.; Dutta, R.; Damnjanovic, R.; Phan, M.-H.; Denmark, D.J.; Biswal, MR.; McGill, A.R.; Green, R.; Howell, M.; Ghosh, P.; Gonzalez, A.; Ahmed, N.T.; Borresen, B.; Farmer, M.; Gaeta, M.; Sharma, K.; Bouchard, C.; Gamboni, D.; Martin, J.; Tolve, B.; Singh, M.; Judy, J.W.; Li, C.; Santra, S.; Daunert, S.; Zeynaloo, E.; Gelfand, R.M.; Lenhert, S.; McLamore, E.S.; Xiang, D.; Morgan, V.; Friedersdorf, L.E.; Lal, R.; Webster, T.J.; Hoogerheide, D.P.; Nguyen, T.D.; D'Souza, M.J.; Çulha, M.; Kondiah, P.P.D.; Martin, D.K. Advances in Translational Nanotechnology: Challenges and Opportunities. Appl. Sci. 2020, 10, 4881.

    021. Vichare, R.; Garner, I.; Paulson, R.J.; Tzekov, R.; Sahiner, N.; Panguluri, S.K.; Mohapatra, S.; Mohapatra, S.S.; Ayyala, R.; Sneed, K.B.; Biswal, MR*. Biofabrication of Chitosan-Based Nanomedicines and Its Potential Use for Translational Ophthalmic Applications. Appl. Sci. 2020, 10, 4189. (*Corresponding author)

  • 020. Das M, Tang X, Han JY, Mayilsamy K, Foran E, Biswal MR, Tzekov R, Mohapatra SS, Mohapatra S. CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies. J Neuroinflammation. 2019 May 31;16(1):115. doi: 10.1186/s12974-019-1499-z. PMID:31151410; PMCID: PMC6544928. 

  • 019. Biswal MR, Prentice HM, Smith GW, Zhu P, Tong Y, Dorey CK, Lewin AS, Blanks JC. Cell-specific gene therapy driven by an optimized hypoxia-regulated vector reduces choroidal neovascularization. J Mol Med (Berl). 2018 Oct;96(10):1107-1118. doi: 10.1007/s00109-018-1683-0. Epub 2018 Aug 13. PMID: 30105447.

    018. Biswal MR*, Justis BD, Han P, Li H, Gierhart D, Dorey CK, Lewin AS. Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress. PLoS One. 2018 Sep 28;13(9):e0203816. doi: 10.1371/journal.pone.0203816. PMID: 30265681; PMCID: PMC6161850. (*Corresponding author)

  • 017. Biswal MR*, Han P, Zhu P, Wang Z, Li H, Ildefonso CJ, Lewin AS. Timing of Antioxidant Gene Therapy: Implications for Treating Dry AMD. Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):1237-1245. doi: 10.1167/iovs.16-21272. PMID: 28241311; PMCID: PMC5338629.

    016. Tong Y, Zhou YL, Zheng Y, Biswal MR, Zhao PQ, Wang ZY. Analyzing cytokines as biomarkers to evaluate severity of glaucoma. Int J Ophthalmol. 2017 Jun 18;10(6):925-930. doi: 10.18240/ijo.2017.06.15. PMID: 28730084; PMCID: PMC5515140.

  • 015. Ahmed CM, Biswal MR, Li H, Han P, Ildefonso CJ, Lewin AS. Repurposing an orally available drug for the treatment of geographic atrophy. Mol Vis. 2016 Apr 2;22:294-310. PMID: 27110092 PMCID: PMC4818958.

    014. Ildefonso CJ, Jaime H, Brown EE, Iwata RL, Ahmed CM, Massengill MT, Biswal MR, Boye SE, Hauswirth WW, Ash JD, Li Q, Lewin AS. Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):372-86. doi: 10.1167/iovs.15-17703. PMID: 26842755; PMCID: PMC5110262.

    013. Ildefonso CJ, Biswal MR, Ahmed CM, Lewin AS. The NLRP3 Inflammasome and its Role in Age-Related Macular Degeneration. Adv Exp Med Biol. 2016;854:59-65. doi: 10.1007/978-3-319-17121-0_9. PMID: 26427394.

    012. Biswal MR, Ildefonso CJ, Mao H, Seo SJ, Wang Z, Li H, Le YZ, Lewin AS. Conditional Induction of Oxidative Stress in RPE: A Mouse Model of Progressive Retinal Degeneration. Adv Exp Med Biol. 2016;854:31-7. doi: 10.1007/978-3-319-17121-0_5. PMID: 26427390.

    011. Berkowitz BA, Lewin AS, Biswal MR, Bredell BX, Davis C, Roberts R. MRI of Retinal Free Radical Production With Laminar Resolution In Vivo. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):577-85. doi: 10.1167/iovs.15-18972. PMID: 26886890; PMCID: PMC4771178.

    010. Tong Y, Zhao KK, Feng D, Biswal MR, Zhao PQ, Wang ZY, Zhang Y. Comparison of the efficacy of anti-VEGF monotherapy versus PDT and intravitreal anti-VEGF combination treatment in AMD: a Meta-analysis and systematic review. Int J Ophthalmol. 2016 Jul 18;9(7):1028-37. doi: 10.18240/ijo.2016.07.16. PMID: 27500113; PMCID: PMC4951659.

  • 009. Ildefonso CJ, Jaime H, Biswal MR, Boye SE, Li Q, Hauswirth WW, Lewin AS. Gene therapy with the caspase activation and recruitment domain reduces the ocular inflammatory response. Mol Ther. 2015 May;23(5):875-884. doi: 10.1038/mt.2015.30. Epub 2015 Feb 20. PMID: 25698151; PMCID: PMC4427880.

    008. Biswal MR, Ahmed CM, Ildefonso CJ, Han P, Li H, Jivanji H, Mao H, Lewin AS. Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and preserves the retina from mitochondrial oxidative stress. Exp Eye Res. 2015 Nov;140:94-105. doi: 10.1016/j.exer.2015.07.022. Epub 2015 Aug 25. PMID: 26315784; PMCID: PMC4624518.

  • 007. Mao H, Seo SJ, Biswal MR, Li H, Conners M, Nandyala A, Jones K, Le YZ, Lewin AS. Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration. Invest Ophthalmol Vis Sci. 2014 Jul 1;55(7):4613-27. doi: 10.1167/iovs.14-14633. PMID: 24985474; PMCID: PMC4112607.

    006. Wang ZY, Zhao K, Zheng J, Rossmiller B, Ildefonso C, Biswal M, Zhao PQ. Systematic review and meta-analysis of the association between complement factor H I62V polymorphism and risk of polypoidal choroidal vasculopathy in Asian populations. PLoS One. 2014 Feb 10;9(2):e88324. doi: 10.1371/journal.pone.0088324. PMID: 24520367; PMCID: PMC3919738.

    005. Biswal MR, Prentice HM, Dorey CK, Blanks JC*. A hypoxia-responsive glial cell-specific gene therapy vector for targeting retinal neovascularization. Invest Ophthalmol Vis Sci. 2014 Nov 6;55(12):8044-53. doi: 10.1167/iovs.14-13932. PMID: 25377223; PMCID: PMC4263136.

  • 004. Wang ZY, Zhao K, Li JK, Biswal MR, Zhao PQ. Immediate corneal vitrectomy for posteriorly dislocated lens fragments during cataract surgery. Retina. 2013 Sep;33(8):1715-9. doi: 10.1097/IAE.0b013e318294782c. PMID: 23807182.

    003. Biswal MR., Singh S.D., Srivastava PP., D Umesha. Molecular Cloning and Characterization of Asian Seabass (Lates calcarifer) Beta-Actin Gene Promoter. National Academy Science Letters. 2012; 35 (3), 163-168.

    002. Prentice HM, Biswal MR, Dorey CK, Blanks JC. Hypoxia-regulated retinal glial cell-specific promoter for potential gene therapy in disease. Invest Ophthalmol Vis Sci. 2011 Nov 1;52(12):8562-70. doi: 10.1167/iovs.10-6835. PMID: 21960554; PMCID: PMC3208

    001. Kumar S. Choudhury D, Baruah K, Biswal MR., D Umesha, Sahu NP. Effect of feeding three different formulated feeds having different protein levels on the growth of angel fish (Pterophyllum scalare) juveniles. Journal of the Indian Fisheries Association. 2005; 32, 95-101.

Additional Publications

A complete list of publications are available through Google Scholar