Vanderbilt University School of Medicine

Brantley, Milam A. , MD, PhD
Associate Professor of Ophthalmology & Visual Sciences
Associate Professor of Molecular Physiology and Biophysics

Lab Url:

Phone Number: 615-936-5679


Brantley, Milam's picture

Office Address   Mailing Address

Langford 11425, MRBIV

Research Specialty
Pharmacogenomics and metabolomics of retinal diseases

Clinical Research Description
Our goal is to develop personalized treatment regimens for patients with degenerative retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and primary open angle glaucoma (POAG). Our current research aims to uncover metabolomic and genetic influences on the development and progression of these blinding diseases. Our work also investigates metabolomic associations with treatment response for AMD.

Genetics and environmental exposures both contribute to the risk of developing AMD and its progression to sight-threatening advanced stages. Because neither genetic variants nor individual molecular biomarkers effectively predict AMD progression or response to treatment, we are using comprehensive metabolic profiling combined with genetic analyses to refine the evaluation of AMD risk. We have performed a metabolome-wide association study (MWAS) of neovascular AMD and have identified individual molecules and molecular pathways that are altered in the disease. We are currently studying these altered metabolites and pathways in a targeted fashion.

Diabetic retinopathy (DR) leads to complications including macular edema and abnormal retinal blood vessel growth. We have recruited over 600 patients from the VEI for a longitudinal study on the metabolomics of diabetic retinopathy. Our initial work has identified pathways, many related to mitochondria, which are altered in Type 2 diabetics with retinopathy compared to controls. We also recently discovered an association between particular mitochondrial haplogroups and severity of diabetic retinopathy. Our current work is investigating the relationship between these metabolic and genetic findings.

We have recently carried out an MWAS of POAG and discovered that carnitines and vitamin D2 metabolites were altered in glaucoma patients compared to controls. Ongoing work is designed to understand the specifics of the carnitine metabolite alterations and how these changes may be related to fatty acid oxidation in the mitochondria.

Clinical Interests
Inherited retinal diseases, genetics of age-related macular degeneration and diabetic retinopathy, ocular pharmacogenomics

Burgess, LG, Uppal, K, Walker, DI, Roberson, RM, Tran, V, Parks, MB, Wade, EA, May, AT, Umfress, AC, Jarrell, KL, Stanley, BO, Kuchtey, J, Kuchtey, RW, Jones, DP, Brantley, MA. Metabolome-Wide Association Study of Primary Open Angle Glaucoma. Invest Ophthalmol Vis Sci, 56(8), 5020-8, 2015.

Estopinal, CB, Chocron, IM, Parks, MB, Wade, EA, Roberson, RM, Burgess, LG, Brantley, MA, Samuels, DC. Mitochondrial haplogroups are associated with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci, 55(9), 5589-95, 2014.

Kuchtey, J, Kunkel, J, Burgess, LG, Parks, MB, Brantley, MA, Kuchtey, RW. Elevated transforming growth factor ??1 in plasma of primary open-angle glaucoma patients. Invest Ophthalmol Vis Sci, 55(8), 5291-7, 2014.

Osborn, MP, Park, Y, Parks, MB, Burgess, LG, Uppal, K, Lee, K, Jones, DP, Brantley, MA. Metabolome-wide association study of neovascular age-related macular degeneration. PLoS One, 8(8), e72737, 2013.

Brantley, MA, Osborn, MP, Sanders, BJ, Rezaei, KA, Lu, P, Li, C, Milne, GL, Cai, J, Sternberg, P. Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration. Am J Ophthalmol, 153(3), 460-467.e1, 2012.

Brantley, MA, Osborn, MP, Sanders, BJ, Rezaei, KA, Lu, P, Li, C, Milne, GL, Cai, J, Sternberg, P. The short-term effects of antioxidant and zinc supplements on oxidative stress biomarker levels in plasma: a pilot investigation. Am J Ophthalmol, 153(6), 1104-9.e2, 2012.

Sheybani, A, Brantley, MA, Apte, RS. Pattern electroretinography in age-related macular degeneration. Arch Ophthalmol, 129(5), 580-4, 2011. PMCID:3159552

Yu, Y, Bhangale, TR, Fagerness, J, Ripke, S, Thorleifsson, G, Tan, PL, Souied, EH, Richardson, AJ, Merriam, JE, Buitendijk, GH, Reynolds, R, Raychaudhuri, S, Chin, KA, Sobrin, L, Evangelou, E, Lee, PH, Lee, AY, Leveziel, N, Zack, DJ, Campochiaro, B, Campochiaro, P, Smith, RT, Barile, GR, Guymer, RH, Hogg, R, Chakravarthy, U, Robman, LD, Gustafsson, O, Sigurdsson, H, Ortmann, W, Behrens, TW, Stefansson, K, Uitterlinden, AG, van Duijn, CM, Vingerling, JR, Klaver, CC, Allikmets, R, Brantley, MA, Baird, PN, Katsanis, N, Thorsteinsdottir, U, Ioannidis, JP, Daly, MJ, Graham, RR, Seddon, JM. Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum Mol Genet, 20(18), 3699-709, 2011. PMCID:3159552

Lee, AY, Kulkarni, M, Fang, AM, Edelstein, S, Osborn, MP, Brantley, MA. The effect of genetic variants in SERPING1 on the risk of neovascular age-related macular degeneration. Br J Ophthalmol, 94(7), 915-7, 2010.

Neale, BM, Fagerness, J, Reynolds, R, Sobrin, L, Parker, M, Raychaudhuri, S, Tan, PL, Oh, EC, Merriam, JE, Souied, E, Bernstein, PS, Li, B, Frederick, JM, Zhang, K, Brantley, MA, Lee, AY, Zack, DJ, Campochiaro, B, Campochiaro, P, Ripke, S, Smith, RT, Barile, GR, Katsanis, N, Allikmets, R, Daly, MJ, Seddon, JM. Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci U S A, 107(16), 7395-400, 2010. PMCID:2867697

Brantley, MA, Edelstein, SL, King, JM, Plotzke, MR, Apte, RS, Kymes, SM, Shiels, A. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy. Eye (Lond), 23(3), 626-31, 2009. PMCID:2704905

Fang, AM, Lee, AY, Kulkarni, M, Osborn, MP, Brantley, MA. Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration. Mol Vis, 15, 2710-9, 2009. PMCID:2793900

Hegedus, B, Hughes, FW, Garbow, JR, Gianino, S, Banerjee, D, Kim, K, Ellisman, MH, Brantley, MA, Gutmann, DH. Optic nerve dysfunction in a mouse model of neurofibromatosis-1 optic glioma. J Neuropathol Exp Neurol, 68(5), 542-51, 2009. PMCID:2746323

Lee, AY, Raya, AK, Kymes, SM, Shiels, A, Brantley, MA. Pharmacogenetics of complement factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol, 93(5), 610-3, 2009. PMCID:2746323

Brantley, MA, Jain, S, Barr, EE, Johnson, EM, Milbrandt, J. Neurturin-mediated ret activation is required for retinal function. J Neurosci, 28(16), 4123-35, 2008. PMCID:2704905

Lee, AY, Brantley, MA. CFH and LOC387715/ARMS2 genotypes and antioxidants and zinc therapy for age-related macular degeneration. Pharmacogenomics, 9(10), 1547-50, 2008. PMCID:2746323

Brantley, MA, Edelstein, SL, King, JM, Apte, RS, Kymes, SM, Shiels, A. Clinical phenotypes associated with the complement factor H Y402H variant in age-related macular degeneration. Am J Ophthalmol, 144(3), 404-408, 2007. PMCID:2140051

Brantley, MA, Fang, AM, King, JM, Tewari, A, Kymes, SM, Shiels, A. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. Ophthalmology, 114(12), 2168-73, 2007. PMCID:2704905

Knopf, HL, Carter, K, Council, MD, Brantley, MA. Peripapillary Hemorrhage. Compr Ophthalmol Update, 8(1), 53-4, 2007. PMCID:2140051

Michaelides, M, Chen, LL, Brantley, MA, Andorf, JL, Isaak, EM, Jenkins, SA, Holder, GE, Bird, AC, Stone, EM, Webster, AR. ABCA4 mutations and discordant ABCA4 alleles in patients and siblings with bull''s-eye maculopathy. Br J Ophthalmol, 91(12), 1650-5, 2007. PMCID:2095527

Zhu, Y, Zhang, Y, Ojwang, BA, Brantley, MA, Gidday, JM. Long-term tolerance to retinal ischemia by repetitive hypoxic preconditioning: role of HIF-1alpha and heme oxygenase-1. Invest Ophthalmol Vis Sci, 48(4), 1735-43, 2007. PMCID:2140051

Feiner, L, Barr, EE, Shui, YB, Holekamp, NM, Brantley, MA. Safety of intravitreal injection of bevacizumab in rabbit eyes. Retina, 26(8), 882-8, 2006. PMCID:2140051

Michaelides, M, Jenkins, SA, Brantley, MA, Andrews, RM, Waseem, N, Luong, V, Gregory-Evans, K, Bhattacharya, SS, Fitzke, FW, Webster, AR. Maculopathy due to the R345W substitution in fibulin-3: distinct clinical features, disease variability, and extent of retinal dysfunction. Invest Ophthalmol Vis Sci, 47(7), 3085-97, 2006. PMCID:2140051

Harbour, JW, Brantley, MA, Hollingsworth, H, Gordon, M. Association between posterior uveal melanoma and iris freckles, iris naevi, and choroidal naevi. Br J Ophthalmol, 88(1), 36-8, 2004. PMCID:1771959

Harbour, JW, Brantley, MA, Hollingsworth, H, Gordon, M. Association between choroidal pigmentation and posterior uveal melanoma in a white population. Br J Ophthalmol, 88(1), 39-43, 2004. PMCID:1771924

Mantel, I, Brantley, MA, Bellmann, C, Robson, AG, Holder, GE, Taylor, A, Anderson, G, Moore, AT. Juvenile neuronal ceroid lipofuscinosis (Batten disease) CLN3 mutation (Chrom 16p11.2) with different phenotypes in a sibling pair and low intensity in vivo autofluorescence. Klin Monbl Augenheilkd, 221(5), 427-30, 2004. PMCID:2140051

Joseph, DP, Brantley, MA, Grand, MG. Serpiginouslike choroiditis in a patient with cardiac sarcoidosis. Retina, 23(1), 116-7, 2003. PMCID:1771959

Brantley, MA, Worley, L, Harbour, JW. Altered expression of Rb and p53 in uveal melanomas following plaque radiotherapy. Am J Ophthalmol, 133(2), 242-8, 2002. PMCID:1771959

Postdoctoral Position Available

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