Lloyd Paul Aiello, M.D., Ph.D.
Dr. Aiello 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 doctoral 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 vitreoretinal and a research fellowship, joining the staff in 1994.
Dr. Aiello is the author of 77 original papers and 133 publications and the recipient of more than 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, Dr. Aiello is committed to eliminating visual loss resulting from diabetic retinopathy (a condition in which abnormal blood vessels grow on the retina) and other related retinopathies. These conditions are usually caused by insufficient blood perfusion with subsequent proliferation of sight-damaging blood vessels and abnormal vessel leakage 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 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, has been Chairman of three multi-center, multi-national, 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). Results from these studies thus far have supported an application to the Food and Drug Administration, which has deemed the drug “Approvable” for this indication pending additional study data.
In related research, Dr. Aiello’s laboratory made significant progress toward understanding and manipulating 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 observed following vitrectomy (surgical replacement of the gel-like substance in the eye with clear 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 Founding Director of the Beetham Eye Institute and Dr. Lloyd P. Aiello’s father.
In other research, Dr. Aiello’s laboratory uncovered portions of the molecular mechanisms by which hypertension exacerbates diabetic retinopathy and has evaluated the effects of diabetes on retinal blood flow with colleagues Allen Clermont and Sven-Erik Bursell, Ph.D.
Selected References
The PKC-DRS2 Study Group. Manuscript Writing & Study Executive Committee: Aiello LP (Chair), Davis MD, Milton RC, Sheetz MJ, Vignati L, Zhi X. Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology [on line] September 19, 2006.
The PKC-DMES Study Group. Manuscript Writing & Study Executive Committee: Aiello LP (Chair), Davis MD, Milton RC, Sheetz MJ. Effect of ruboxistaurin, a PKC b isoform-selective inhibitor, in patients with diabetic macular edema: 30-month results of the randomized PKC-DMES clinical trial. Ophthalmology 2006,
Clermont AC, Cahill M, Salti H, Rook SL, Rask-Madsen C, Goddard L, Wong JS, Bursell D, Bursell SE, Aiello LP. Hepatocyte growth factor induces retinal vascular permeability via MAP-kinase and PI-3 kinase without altering retinal hemodynamics. Invest Ophthalmol Vis Sci 47:2701-2708, 2006.
Aiello LP, Clermont A, Arora V, Davis MD, Sheetz MJ, Bursell SE. Inhibition of PKC b# by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Invest Ophthalmol Vis Sci 47:86-92, 2006.
The PKC-DRS Study Group. Manuscript Writing & Study Executive Committee: Aiello LP (Chair), Davis MD, Milton RC, Sheetz MJ, Arora V, Vignati L. The Effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C b Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes 54:2188-2197, 2005.
Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LEH. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A 92:10457-10461,1995.
Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480-1487, 1994.
