Ram Kannan, PhD, FARVO

Oxidative stress, antioxidant defense, membrane transporters, mitochondrial function, retinal pigment epithelium, age related macular degeneration (AMD), senescence, nanotherapy

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in individuals over age 55 in the United States. Basic and clinical studies implicate the retinal pigment epithelium (RPE) as a primary site of pathology in the disease. Our research over the years has centered on antioxidative mechanisms in RPE and the retina and preventive modalities of retinal dysfunction in ocular diseases. These investigations use newer models of experimental AMD and have generated novel therapeutic approaches for the prevention of atrophic and neovascular AMD in particular with novel elastin like nanoparticles of endogenous and exogenous substrates.

Our focus has been on the role of specific and novel mitochondrial peptides (alphaB crystallin, humanin, and HM 10/10) in ameliorating mitochondrial dysfunction in oxidative injury to RPE and neural retina. Our new and recent research emphasis is on the mechanisms of deposition of oxidized lipids and lipoproteins via oxidative stress and complement activation in the pathophysiology of the choroid mouse models of lipoprotein deficiency and devising therapeutic approaches. Our lab is also actively engaged in research on the emerging role of senescence in AMD and in the development of novel senolytic drugs.

Sreekumar PG, Kannan R. Mechanisms of protection of retinal pigment epithelial cells from oxidant injury by humanin and other mitochondrial-derived peptides: Implications for age-related macular degeneration. Redox Biol. 2020 Oct;37:101663. doi: 10.1016/j.redox.2020.101663. Epub 2020 Jul 29. PMCID: PMC7767738

Sreekumar PG, Wang M, Spee C, Sadda SR, Kannan R. Transporter-Mediated Mitochondrial GSH Depletion Leading to Mitochondrial Dysfunction and Rescue with αB Crystallin Peptide in RPE Cells. Antioxidants (Basel). 2020 May 12;9(5):E4111. doi:10.3390/antiox9050411. PMCID: PMC7278883

Kaarniranta K, Uusitalo H, Blasiak J, Felszeghy S, Kannan R, Kauppinen A, Salminen A, Sinha D, Ferrington D. Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. Prog Retin Eye Res. 2020 Apr 13:100858. doi: 10.1016/j.preteyeres.2020.100858. Online ahead of print. PMCID: PMC7650008

Sreekumar PG, Hinton DR, Kannan R. The emerging role of senescence in ocular disease. Oxid Med Cell Longev. 2020 Mar 9;2020:2583601 Published online 2020Mar 9. doi: 10.1155/2020/2583601. eCollection 2020. PMCID: PMC7085400

Su F, Spee C, Araujo E, Barron E, Wang M, Ghione C, Hinton DR, Nusinowitz S, Kannan R, Reddy ST, Farias-Eisner R. A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration. Int J Mol Sci. 2019 Sep 27;20(19). PMCID: PMC6801888

Wang M, Lau LI, Sreekumar PG, Spee C, Hinton DR, Sadda SR, Kannan R. Characterization and Regulation of Carrier Proteins of Mitochondrial Glutathione Uptake in Human Retinal Pigment Epithelium Cells. Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):500-516. doi: 10.1167/iovs.18-25686. PMCID: PMC636099

Felszeghy S, Viiri J, Paterno JJ, Hyttinen JMT, Koskela A, Chen M, Leinonen H, Tanila H, Kivinen N, Koistinen A, Toropainen E, Amadio M, Smedowski A, Reinisalo M, Winiarczyk M, Mackiewicz J, Mutikainen M, Ruotsalainen AK, Kettunen M, Jokivarsi K, Sinha D, Kinnunen K, Petrovski G, Blasiak J, Bjørkøy G, Koskelainen A, Skottman H, Urtti A, Salminen A, Kannan R, Ferrington DA, Xu H, Levonen AL, Tavi P, Kauppinen A, Kaarniranta K. Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration. Redox Biol. 2019 Jan;20:1-12. doi: 10.1016/j.redox.2018.09.011. Epub 2018 Sep 14. PMCID: PMC6156745

Sreekumar PG, Li Z, Wang W, Spee C, Hinton DR*, Kannan R, MacKay JA. Intra-vitreal αB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration. J Control Release. 2018 Aug 10;283:94-104. doi: 10.1016/j.jconrel.2018.05.014. Epub 2018 May 18. PMCID: PMC6368441.

Minasyan L, Sreekumar PG, Hinton DR, Kannan R. Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in Oxidative and Endoplasmic Reticulum Stress in RPE Cells. Oxid Med Cell Longev. 2017;2017:1675230. doi: 10.1155/2017/1675230. Epub 2017 Jul 26. Review. PMCID: PMC5549471

Ishikawa K, Sreekumar PG, Spee C, Nazari H, Zhu D, Kannan R, Hinton DR. αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition. Am J Pathol. 2016 Apr;186(4):859-73. doi: 10.1016/j.ajpath.2015.11.014. Epub 2016 Feb 12. PMCID: PMC4822331

Wang W, Sreekumar PG, Valluripalli V, Shi P, Wang J, Lin YA, Cui H, Kannan R, Hinton DR, MacKay JA. Protein polymer nanoparticles engineered as chaperones protect against apoptosis in human retinal pigment epithelial cells. J Control Release. 2014 Oct 10;191:4-14. doi: 10.1016/j.jconrel.2014.04.028. Epub 2014 Apr 26.  PMCID: PMC4222838

Kannan R, Sreekumar PG, Hinton DR. Novel roles for α-crystallins in retinal function and disease. Prog Retin Eye Res. 2012 Nov;31(6):576-604. doi: 10.1016/j.preteyeres.2012.06.001. Epub 2012 Jun 18. Review.  PMCID: PMC3472046

Fellow of the Association for Research in Vision and Ophthalmology (FARVO)
Study Section member NIH, NSF
Board of Scientific Counselors, Intramural NEI NIH
Visiting Professor, Zhengzhou Eye Institute (China)
Veteran’s Administration Merit Award
Gold Medalist, Government of India Scholarship