Age-related macular degeneration (AMD) is a leading cause of vision loss in Americans over the age of 50 and involves the degeneration of the small, central portion of the retina, known as the macula. The cause of AMD is largely unknown and so it is critical to understand the pathogenesis of the disease to develop new prevention or therapeutic strategies.
Gerard A. Lutty, PhD, Director, Ocular Vasculogenesis and Angiogenesis Laboratory and Professor of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital
Gerard Lutty, PhD, a professor of Ophthalmology at the Wilmer Ophthalmological Institute at Johns Hopkins Hospital, and his team are investigating the changes that occur in the choroidal vasculature following AMD. Loss of blood vessel supply to the retina can result in death of retinal cells and contribute to disease progression. Dr. Lutty’s group has evaluated the loss of the small choroidal capillaries (choriocapillaris) in AMD using human donor tissue. They have found that choriocapillaris die early on in wet AMD, making the retinal pigment epithelium (RPE) hypoxic and a source of VEGF. In geographic atrophy, a form of dry AMD, the RPE die first and then the choriocapillaris. The goal of this work is to develop therapies for AMD that would stop the loss of these blood vessels in the affected area.
In addition to AMD, Dr. Lutty’s group studies the development of blood vessels in the eye and how they are impacted in other ocular diseases, such as diabetic and sickle cell retinopathies.
Bhutto, I.A., McLeod, D.S., Merges, C., Hasegawa, T., Lutty, G.A. Localization of SDF-1 and CXCR4 in retina and choroid of aged human eyes and in eyes with age-related macular degeneration. Brit. J. Ophthalmol. 90:906-910, 2006. PMCID:PMC1857162
Bhutto IA, Uno K, Merges C, Zhang L, McLeod DS, Lutty GA. “Endogenous angiogenesis inhibitors are reduced in Bruch’s membrane of the submacular region in eyes with age-related macular degeneration (AMD).” Arch Ophthalmol 126:670-678, 2008. PMID:18474778
McLeod DS, Grebe R, Bhutto I, Merges C, Baba T, Lutty GA. “Relationship between RPE and choriocapillaris in age-related macular degeneration.” Invest. Ophthalmol. Vis. Sci. 2009, Oct 50(10):4982 - 4991. epub 2009 April 8. PMID:19357355
Barcelona P, Luna JD, Chiabrando GA, Juarez CP, Bhutto IA, Baba T, McLeod DS, Sánchez MC, Lutty GA. “Immunohistochemical localization of low density lipoprotein receptor-related protein 1 and α2-macroglobulin in human retinal and choroidal tissue of proliferative retinopathies. Exp. Eye Res. 2010;91:264-72. PMCID:PMC2907439
Bhutto I, Baba T, Merges C, Juriasinghani V, McLeod DS, Lutty GA. C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration (AMD). Brit J Ophthalmol, 2011;95:1323-1330.
McLeod DS, Baba T, Bhutto IA, Lutty GA. Co-expression of Endothelial and Neuronal Nitric Oxide Synthases in the Developing Vasculatures of the Human Fetal Eye. Graefes Arch Clin Exp Ophthalmol 2012;250:839-848. PMCID:PMC3358532
Bhutto I, Lutty GA. Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex. Molecular Aspects of Medicine 2012;33:295-317.(NIHMS 384160)(PMCID: PMC3392421)
Edwards MM, McLeod DS, Bhutto I, Hardin A, Seddon J, Lutty GA. Idiopathic preretinal glial blooms in aged eyes and in age-related macular degeneration. Exp. Eye Res. 2015 S0014-4835(15)00242-0. doi: 10.1016/j.exer.2015.07.016. [Epub ahead of print] PMID: 26220834
Bhutto IA, McLeod DS, Jing T, Sunness JS, Seddon JM, Lutty GA. Increased choroidal mast cells and their degranulation in age-related macular degeneration. Brit. J. Ophthalmol. 100: 720-726, 2016. doi:10.1136/bjophthalmol-2015-308290
Seddon J, McLeod DS, Bhutto IA, Villalonga MB, Silver RE, Wenick A, Edwards ME, Lutty GA. Histopathological Insights into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration. JAMA Ophthalmol. 2016: 134:1272-1280.
Rodrigues M, Kashiwabuchi F, Deshpande M, Jee K, Goldberg MF, Lutty G, Semenza GL, Montaner S, Sodhi A. Expression of HIF1 and VEGF supports circumferential application of scatter laser for proliferative sickle cell retinopathy. Invest Ophthalmol Vis Sci 2016:57:6739-6746.
McLeod DS, Bhutto I, Edwards MM, Silver RE, Seddon JM, Lutty GA. Distribution and Quantification of Choroidal Macrophages in Human Eyes with Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 2016: 57:5843-5844.