Age-related macular degeneration, AMD, mitochondrial genetics, Keratoconus, KC
AS A GRADUATE STUDENT:
University of Arizona, Society of Sigma Xi, 1973.
University of Arizona, Society of Sigma Xi, 1974.
University of Arizona, Society of Sigma Xi, 1976.
University of Arizona Foundation Award for Meritorious Performance in Teaching, 1976.
AS A MEDICAL STUDENT:
Emil Bogan Research Prize for Outstanding Research as a Medical Student, 1987, University of California, Los Angeles.
Solomon Scholar Award for Medical Research, 1988, Cedars-Sinai Medical Center and University of California, Los Angeles.
Solomon Scholar Award for Medical Research, 1989, Cedars-Sinai Medical Center and University of California, Los Angeles.
Paul Rubenstein Award for Research, 1989, Cedars-Sinai Medical Center, Los Angeles.
AS A FACULTY MEMBER:
Kaiser Permanente Award for Excellence in Teaching, 1980, Univ of California, Davis.
Invited speaker at the ARVO Protease Symposium, 1993, Sarasota .FL.
Everett Kinsey Lecture presented at 1999 CLAO Annual Meeting, Las Vegas NV.
Whitney Sampson Invited Speaker 2006, CLAO Annual Meeting, Las Vegas, NV.
Global Keratoconus International Meeting 2007, Invited Speaker, Las Vegas, NV
Mitochondrial Genetics in Age-related Macular Degeneration – We have used molecular and biochemical studies to identify the role of mitochondria in the development and progression of age-related macular degeneration (AMD). We discovered that retinas from AMD patients had several genetic mitochondrial DNA (mtDNA) defects and that their mitochondria were highly damaged compared to normal retinas. When mitochondria are damaged then energy production is decreased and the cell can undergo apoptosis or programmed cell death. My laboratory uses the transmitochondrial cybrid (cytoplasmic hybrid) model, where all cells have identical nuclei, but differ in their mtDNA content to compare mitochondria from AMD versus age-matched normal subjects. We find that the cybrids containing AMD mitochondria have higher levels of apoptosis, autophagy and inflammation compared to the normal cybrids. These degenerative pathways can be blocked by treatment with humanin-G, a mitochondrial derived peptide. Our cybrid model allows us to identify important mitochondria-targeting drugs and peptides to treat age-related retinal diseases.
Role of Mitochondria in Ethnic/Racial Susceptibility Differences to Diseases and Responses to Medications – African-origin populations are more susceptible to diabetes and other age-related diseases compared to European-origin populations, but mechanisms for the differential susceptibility remain unknown. Human mitochondrial (mt) DNA haplogroups, as defined by accumulations of single nucleotide polymorphisms (SNPs), are maternally inherited ancient polymorphisms representing geographic origins of populations. Several studies have shown that Type 2 diabetes and its complications can be linked to mtDNA haplogroup subsets. In the past, it has been difficult to assign functional consequences to the different mtDNA haplogroups. However, my laboratory can now be addresses this question using the transmitochondrial cybrid (cytoplasmic hybrid) model, where all cells have identical nuclei, but differ in their mtDNA content. Our studies provide evidence that cybrids containing African-origin (L) haplogroup mtDNA have significantly different bioenergetic profiles, production levels of reactive oxygen species, and expression levels for complement, inflammation, apoptosis, WNT pathway and diabetes-related genes compared to the European-origin H cybrids. Our findings support the hypothesis that an individual’s mtDNA haplogroup background acts as a “modifier” for the expression of diabetes-related genes, thereby contributing to the ethnic/racial disparities associated with Type 2 diabetes and its complications.
Keratoconus Research – We have also applied the mitochondrial medicine approach to the corneal disease called keratoconus (KC). My laboratory has demonstrated that KC corneas and cultured cells have signs of oxidative damage including damage to the mitochondrial DNA (mtDNA), altered levels of antioxidant enzymes, and accumulations of cytotoxic reactive oxygen/nitrogen species (ROS/RNS). In addition the isolated, cultured KC cells show an increased sensitivity to oxidative stress and cannot eliminate the cytotoxic elements as efficiently as age-matched normal corneal cells. These data support Dr. Kenney’s overall hypothesis that oxidative stress, including mitochondrial damage and ROS/RNS production, are factors that may contribute to development and progression of keratoconus.
142. 2017 Kerur N, Fukuda S, Banerjee D, Kim Y, Fu D, Apicella I, Varshney A, Yasuma R, Fowler BJ, Baghdasaryan E, Marion KM, Huang X, Yasuma T, Hirano Y, Serbulea V, Ambati M, Ambati VL, Kajiwara Y, Ambati K, Hirahara S, Bastos-Carvalho A, Ogura Y, Terasaki H, Oshika T, Kim KB, Hinton DR, Leitinger N, Cambier JC, Buxbaum JD, Kenney MC, Jazwinski SM, Nagai H, Hara I, West AP, Fitzgerald KA, Sadda SR, Gelfand BD, Ambati J. cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nature Medicine. 2017 Nov 27. doi: 10.1038/nm.4450. PMID:29176737
141. 2017 Udar N, Atilano SR, Boyer DS, Chwa M, Memarzadeh M, Langberg J, Nesburn AB, Hertzog D, Kenney MC. CKMT2 mutation in a patient with fatigue, age-related macular degeneration, deafness and atrial fibrillation. Biomed Genet Genomics, 2017 doi: 10.15761/BGG.1000133
140. 2017 Moustafa MT, Ramirez C, Schneider K, Atilano SR, Limb GA, Kuppermann BD, Kenney MC. Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Müller Cells. J Ocul Pharmacol Ther. 2017 Oct:33(8):610-619. doi: 10.1089/jop.2016.0129. PMID: 28961056. (Impact factor 1.42)
139. 2017 Riazi-Esfahani M, Kuppermann BD, Kenney MC. The Role of Mitochondria in AMD: Current Knowledge and Future Applications. J Ophthalmic Vis Res. 12(4):424-428. doi: 10.4103/jovr.jovr_182_17. PMID: 29090054. (Impact factor 0.77)
138. 2017 Nashine S, Cohen P, Chwa M, Lu S, Nesburn AB, Kuppermann BD, Kenney MC. Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis. 20;8(7):e2951. doi: 10.1038/cddis.2017.348. PMID:28726777
137. 2016 Nashine S, Chwa M, Kazemian M, Thaker K, Lu S, Nesburn AB, Kuppermann BD, Kenney MC. Differential expression of complement markers in Normal and AMD transmitochondrial cybrids. PLoS ONE. 2016 Aug 3;11 8:e0159828. doi: 10.1371. PMID: 27486856
136. 2016 Thaker K, ChwA M, Atilano SR, Coskun P, Cáceres-del-Carpio J, Udar N, Boyer DS, Jazwinski SM, Miceli MV, Nesburn AB, Kuppermann BD and Kenney MC. Increased expression of ApoE and protection from Amyloid-beta toxicity in transmitochondrial cybrids with haplogroup K mtDNA. Neurobiol Dis. 2016 Apr 21. pii: S0969-9961(16)30078-X. doi: PMID: 27109188
135. 2016 Gupta NK, Mansoor S, Sapkal AU, A Limb A, Kuppermann BD and Kenney MC. Effects of Benzo(e)Pyrene, a toxic component of cigarette smoke, on Muller Cells (MIO-M1) in vitro. New Front Ophthalmol, 2016 doi: 10.15761/NFO.1000124.
134. 2016 Kenney MC, Falatoonzadeh P, Atilano SR, Chwa M, Caceres-del-Carpio J, Malik D, Boyer DS, Nesburn AB and Kuppermann BD. African-origin mitochondrial DNA variants as a contributing factor to susceptibilities for diabetes and age-related diseases. Int J Diabetes Clin Res. 3:053. ISSN: 2377-3634
133. 2016 Ferrington DA, Kapphahn RJ, Leary MM, Atilano SR, Terluk MR, Karunadharma P, Chen GK, Ratnapriya R, Swaroop A, Montezuma SR, Kenney MC. Increased retinal mtDNA damage in the CFH variant associated with age-related macular degeneration. Exp Eye Res. 145:269-277. doi: 10.1016 PMID: 26854823
132. 2016 Ramírez C, Cáceres-Del-Carpio J, Chu J, Chu J, Moustafa MT, Chwa M, Limb GA, Kuppermann BD, Kenney MC. Brimonidine can prevent in vitro Hydroquinone damage on retinal pigment epithelium cells and retinal Müller cells (MIO-M1). J Ocul Pharmacol Ther. 32(2):102-8. doi: 10.1089/jop.2015.0083. Epub 2015 Dec 1. PMID: 26624556
131. 2015 Mansoor S, Sharma A, Cáceres-del-Carpio J, Zacharias LC, Patil AP, Gupta N, Limb GA, Kenney MC, Kuppermann BD. Effects of light on retinal pigment epithelial cells, neurosensory retinal cells, and Müller cells treated with Brilliant Blue G. Clinical and Experimental Ophthalmology. Dec;43(9):820-9. doi: 10.1111. PMID: 26126999.
130. 2015 Atilano SR, Malik D, Chwa M, Cáceres-del-Carpio J, Nesburn AB, Boyer DS, Kuppermann BD, Jazwinski SM, Miceli MV, Wallace DC, Udar N, Kenney MC. Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes. Human Molecular Genetics. Aug 15;24(16):4491-503. doi: 10.1093/hmg/ddv173. Epub 2015 May 10. PMID: 25964427.
129. 2015 Nalbandian A, Llewellyn K, Gomez A, Walker N, Su H, Dunnigan A, Vesa J, Chwa M, Kenney MC, Kimonis VE. In vitro studies in VCP-associated multisystem proteinopathy suggest altered mitochondrial bioenergetics. Mitochondrion. 22:1-8. PMID: 25724235
128. 2014 Kuppermann BD, Zacharias LC, Kenney MC. Steroid differentiation: the safety profile of various steroids on retinal cells in vitro and their implications for clinical use (an American Ophthalmological Society thesis). Trans American Ophthalmology Society. Jul;112:116-41. PMID:25646032.
127. 2014 Malik D, Tarek M, Cáceres-del-Carpio J, Ramirez C, Boyer D, Kenney MC, Kuppermann BD. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture. British Journal Ophthalmology. Jun;98 Suppl 1:i11-16. PMID:24836865.
126. 2014 Malik D, Cáceres-del-Carpio J, Tarek M, Falatoonzadeh P, Hsu Y, Chwa M, Atilano SR, Ramirez C, Nesburn AB, Boyer DS, Kuppermann BD, Jazwinski SM, Miceli MV, Wallace DC, Udar N, Kenney MC. Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: Implications for retinal diseases. PLoS ONE. 11:9(2):e99003. PMID:24919117.
125. 2014 Kenney MC, Chwa M, Atilano SR, Falatoonzadeh P, Ramirez C, Malik D, Tarek M, Cáceres-del-Carpio J, Nesburn AB, Boyer DS, Kuppermann BD, Vawter M, Jazwinski SM, Miceli M, Wallace DC, Udar N. Inherited mitochondrial DNA variants can affect complement, inflammation, and apoptosis pathways: Insights into mitochondrial-nuclear interactions. Human Molecular Genetics. 23(13):3537-51.PMID:24584571.
124. 2014 Mansoor S, Gupta N, Falatoonzadeh P, Kuppermann BD, Kenney MC. 2-Ethylpyridine, a cigarette smoke component, causes mitochondrial damage in human retinal pigment epithelial cells in vitro. Indian J Ophthalmol. 62(1):16-22. PMID:24492497
123. 2014 Kenney MC, Chwa M, Atilano SR, Falatoonzadeh P, Ramirez C, Malik D, Tarek M, Cáceres-del-Carpio J, Nesburn AB, Boyer DS, Kuppermann BD, Jazwinski SM, Micelli M, Wallace DC, Udar N. Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: Implications for population susceptibility to diseases. Biochim Biophys Acta. Molecular Basis for Disease. 1842(2):208-219. PMID:24200652
122. 2014 Sharma A, Patil JA, Estrago-Franco F, Mansoor S, Raymond V, Kenney MC, Kuppermann BD. Effects of triamcinolone acetonide on human trabecular meshwork cells in vitro. Indian J Ophthalmology 62(4):429-36. PMID:24817746
121. 2013 Kenney MC, Deborah A. Ferrington, Nitin Udar, Mitochondrial Genetics of Retinal Diseases. Retina 5th Edition. Editors: Stephen J. Ryan MD, Andrew P. Schachat MD, Charles P. Wilkinson MD, David R Hinton MD, Srinivas Sadda MD, Peter Wiedemann.
120. 2013 Zacharias LC, Damico FM, Kenney MC, Gasparin F, Acquesta FB, Ventura DF, Takahashi WY, Kuppermann BD. In vitro evidence for mycophenolic acid dose-related cytotoxicity in human retinal cells. Retina 33(10):2155-61. PMID:23615344
119. 2013 Chang M, Bany-Mohammed F, Kenney MC, Beharry KD. Effects of a superoxide dismutase mimetic on biomarkers of lung angiogenesis and alveolarization during hyperoxia with intermittent hypoxia. Am J Transl Res. 5(6):594-607.PMID:24093057
118. 2013 Ramírez C, Pham K, Estragó Franco MF, Chwa M, Limb A, Kuppermann BD, Kenney MC. Hydroquinone induces oxidative and mitochondrial damage to human retinal Müller cells (MIO-M1). Neurotoxicology. 39:102-108. . PMID:23994029
117. 2013 Luthra S, Sharma A, Dong J, Neekhra A, Gramajo AL, Seigel GM, Brown DJ, Kenney MC, Kuppermann BD. Effect of bevacizumab (AvastinTM) on mitochondrial function of in vitro retinal pigment epithelial, neurosensory retinal and microvascular endothelial cells. Indian J Ophthalmol. 61(12):705-10. PMID:24413824
116. 2013 Sharma A, Patil JA, Estrago-Franco F, Mansoor S, Raymond V, Kenney MC, Kuppermann BD. Effects of triamcinolone acetonide on human trabecular meshwork cells in vitro. Indian J Ophthalmol. In Press. PMID:24212220
115. 2013 Gupta N, Mansoor S, Sharma A, Sapkal A, Sheth J, Falatoonzadeh P, Kuppermann BD, Kenney MC. Diabetic Retinopathy and VEGF. Open Ophthalmol J. 7:4-10. PMID:23459241
2007-2008 Discovery Eye Foundation/ Lincy Foundation, “Genetics of Age-Related Macular Degeneration,” $250,000.
2008 Ko Family Foundation “Studies on Diabetic Retinopathy,” $10,000.
2008-2009 Discovery Eye Foundation/Isabel Horn Estate, Genetics of Age-Related Macular Degeneration,” $144,000.
2002-2006 Discovery Eye Foundation and Iris and B. Gerald Cantor Foundation, Aquaporins in Diabetic Retinopathy, $150,000 per year
2006-2007 Discovery Eye Foundation/Lincy Foundation, Genetics of Age-Related Macular Degeneration, $200,000
2006-2007 Discovery Eye Foundation/Pearle Vision Foundation, The Molecular Regulation of Aquaporins to Eliminate Diabetic Macular Edema, $16,000
2007-2008 Discovery Eye Foundation/ Lincy Foundation, Genetics of Age-Related Macular Degeneration, $250,000
2008 Ko Family Foundation, Studies on Diabetic Retinopathy, $10,000.
2008-2009 Discovery Eye Foundation/Isabel Horn Estate, Genetics of Age-Related Macular Degeneration, $144,000
2008-2010 Discovery Eye Foundation/Lincy Foundation, Advanced Genetic Analyses of Age-Related Macular Degeneration (AMD)—Focusing on Mitochondrial Genetic Defects, $356,000
2009-2010 Polly and Michael Smith Foundation, Studies on Age-Related Macular Degeneration (AMD), Co-PI’s - Kuppermann, Klassen and Kenney, $100,000
2010-2011 Beckman Initiative for Macular Research, Association of Mitochondrial Haplogroups with Age-related Macular Degeneration, $75,000
2010-2011 Discovery Eye Foundation/Sussman Foundation, Genetics of Age-Related Macular Degeneration (AMD), $50,000
2010-2011 Discovery Eye Foundation/ Argyros Foundation, Genetic Studies of Age-related Macular Degeneration, $5,000
2010-2011 Polly and Michael Smith Foundation, Studies on Age-Related Macular Degeneration (AMD), Kenney, $30,000
2010-2011 Beckman Initiative for Macular Research, Examining the Interaction between mtDNA Damage, Genetic Risk Factors, and Development of AMD, Kenney-collaborator, Deborah Ferrington - Principal investigator, $15,000
2010-2011 Research to Prevent Blindness, Medical Student Award for Janelle Marshall, $30,000
2011-2012 Polly and Michael Smith, Studies on Age-Related Macular Degeneration (AMD), $30,000
2012-2013 Discovery Eye Foundation, Genetics of Age-Related Macular Degeneration (AMD), $200,000
2013-2014 Discovery Eye Foundation, Genetics of Age-Related Macular Degeneration (AMD), $140,000
2013-2014 Beckman Initiative for Macular Research, Role of Mitochondria in Dry AMD. Kenney - Co-investigator. Kuppermann –Principal investigator, $100,000
2014-2018 Discovery Eye Foundation, private bequest, Genetics of Age-Related Macular Degeneration (AMD). $505,000
2013-2018 Polly and Michael Smith, Mitochondrial Dysfunction in Dry AMD. $120,000
2016-2018 Edith and Roy Carver Foundation, Screening Novel Therapies for the Dry Form of Age-related Macular Degeneration Using ‘Personalized’ Transmitochondrial Cybrids, $125,000
2016-2017 Research to Prevent Blindness, Medical Student Award for Thomas Vo, MS-III, Role of Mitochondrial-derived Peptide Humanin in Patients with Age-related Macular Degeneration, $30,000
2017 Ayala School of Medicine Pilot Award, Investigations of Human Photopigment Opsin Gene Variations and Age-related Macular Degeneration (AMD), $48,724
Association for Research in Vision and Ophthalmology
American Academy of Ophthalmology,
Los Angeles County Women’s Medical Association –
Women in Ophthalmology
LA Research Study Club
Contact Lens Association of Ophthalmologists (CLAO)
Orange County Society of Ophthalmology
Adjunct Associate Professor
Dept. of Anatomy and Cell Biology, UCLA Medical School, Los Angeles, CA 1993—1997
Board Member - Research Director
Discovery Eye Foundation 1985—Pres
Research Scientist II – IV (equivalent to full professor)
Cedars-Sinai Medical Center, Los Angeles, CA 1985—2002
Half-time Research Associate
Department of Anatomy, School of Medicine, University of California, Davis 1983—1985
Department of Anatomy, School of Medicine, University of California, Davis 1978—1983
Lecturer II, Department of Anatomy,
School of Medicine, University of California, Davis, CA 1977—1978
Professor, Department of Ophthalmology,
School of Medicine, UC Irvine, CA 2002—pres
Gavin Herbert Eye Institute