Lloyd P. Aiello, M.D., Ph.D.
Lloyd Paul Aiello, M.D., Ph.D., is Head of Joslin’s Section on Eye Research, Director of Joslin Clinic’s Beetham Eye Institute and Associate Professor of Ophthalmology at Harvard Medical School. Dr. Aiello received his medical and doctorate degrees in Biochemistry from Boston University School of Medicine. He did his residency in ophthalmology at the Wilmer Ophthalmological Institute at Johns Hopkins University and Hospital before coming to the Joslin Diabetes Center, where he completed a clinical vitreo-retinal and a research fellowship, joining the staff in 1994.
Dr. Aiello is the author of more than 60 original papers and over 100 publications and the recipient of 20 national and international awards. He has served as Chair for two Medical Science Review Committees of the Juvenile Diabetes Research Foundation, the American Diabetes Association Lions SightFirst Diabetic Retinopathy Research Program and the National Institutes of Health sponsored Diabetic Retinopathy Clinical Research Network.
A third-generation Joslin ophthalmologist, Lloyd Paul Aiello, M.D., Ph.D., is committed to eliminating visual loss resulting from diabetic retinopathy (a condition in which abnormal blood vessels grow on the retina) and other ischemic (reduced blood flow) retinopathies. These conditions are usually caused by insufficient blood perfusion with subsequent proliferation of sight-damaging blood vessels in the retina. Dr. Aiello’s research aims to determine the biochemistry and molecular mechanisms underlying early diabetic retinopathy and other retinal vascular disorders, including certain retinal tumors and more advanced complications of retinal and macular diseases. Together, these conditions account for the majority of blindness among all working-age individuals in America and other developed countries.
In 2002, Dr. Aiello and several Joslin scientists—including George L. King, M.D., Head of the Section on Vascular Cell Biology—published the first evidence that protein kinase C-beta (PKC-beta) is involved in excessive blood-vessel growth and diabetic retinopathy. The discovery led the scientists to develop a PKC-beta inhibitor that interrupts the actions of this protein.
Dr. Aiello, recognized internationally for his leadership in diabetic retinopathy, is Chairman of three multicenter, multinational, phase 3 clinical trials using this PKC-beta inhibitor. The results will determine whether the inhibitor, which is given orally, can delay or prevent development of the sight-threatening conditions of proliferative diabetic retinopathy or diabetic macular edema (swelling of the retinal tissue caused by leaking blood vessels).
In related research, Dr. Aiello’s laboratory made significant progress toward understanding and controlling the expression, regulation and signaling functions of vascular endothelial growth factor (VEGF) and its receptors. Several years ago, Drs. King and Aiello reported that VEGF, a major growth factor for blood vessels, is elevated in the eye fluids of patients with diabetes who have proliferative retinopathy.
Dr. Aiello’s research has focused extensively on understanding the mechanisms of VEGF expression. For instance, his laboratory found that there are signaling mechanisms for this growth factor in retinal cells, and that factors influencing the expression of VEGF include hypoxia (lack of oxygen), high glucose, diabetes and basic fibroblast growth factor (bFGF), a mediating growth factor.
Dr. Aiello also determined that increased levels of VEGF are normalized when proliferative retinopathy is in remission, as the result of vitrectomy (replacing the gel-like substance in the eye with fluid) or panretinal laser photocoagulation of the retina#a treatment pioneered at Joslin by W.P. Beetham, M.D., and Lloyd M. Aiello, M.D., the Director of the Beetham Eye Institute and Dr. Lloyd P. Aiello’s father.
In other research, Dr. Aiello’s laboratory uncovered the molecular mechanisms by which hypertension exacerbates diabetic retinopathy.
Aiello LP, George DJ, Cahill MT, Wong JS, Cavallerano JD, Hannah AL, Kaelin WG. Rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome following systemic therapy with VEGF receptor inhibitor SU5416. Ophthalmology 109:1745-1751, 2002.
Suzuma I, Suzuma K, Ueki K, Hata Y, Feener EP, King GL, Aiello LP. Stretch-induced retinal VEGF expression is mediated by phosphatidylinositol 3-kinase and protein kinase C (PKC)-zeta but not by stretch-induced ERK1/2, Akt, Ras, or classical/novel PKC pathways. J Biol Chem 277:1047-1057, 2002.
Aiello LP, Bursell SE, Clermont A, Duh E, Ishii H, Takagi C, Mori F, Ciulla TA, Ways K, Jirousek M, Smith LEH, King GL. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta isoform-selective inhibitor. Diabetes 46:1473-1480, 1997.