Researcher Stories

Vascular Pathology of AMD

Understanding vascular pathology of age-related macular degeneration

Gerard A. Lutty, PhD, Director, Ocular Vasculogenesis and Angiogenesis Laboratory and Professor of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital

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.

lutty microscope

lutty microscope

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.

“I could not continue in science without the services provided by NDRI. The human eyes we purchase from NDRI are the backbone of our research into the etiology of diabetic and sickle cell retinopathy as well as age-related macular degeneration. The human eyes we have received have resulted in more than 30 manuscripts from my lab.”      

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.

Recent Publications

Uno, K., Bhutto, I.A., McLeod, D.S., Merges, C., and Lutty, G.A. Impaired expression of thrombospondin-1 in eyes with age-related macular degeneration. Brit. J. Ophthalmol. 90:48-54, 2006.

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

Bhutto IA, Baba T, Merges C, McLeod DS, Lutty GA. “Low nitric oxide synthases (NOSs) in eyes with age-related macular degeneration(AMD).” Exp Eye Res. 2010; 90:155-67. PMCID:PMC2789190

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)

Lutty GA. Effects of diabetes on the eye. Invest Ophthalmol Vis Sci. 2013 54(14):ORSF81-7. doi: 10.1167/iovs.13-12979. PMID: 24335073 PMCID:PMC3864380

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.

Edwards MM, McLeod DS, Bhutto IA, Grebe R, Duffy M, Lutty GA. Subretinal glial membranes in eyes with Geographic Atrophy. Invest Ophthalmol Vis Sci 2017.58:1352-1367.

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