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  Joslin Investigator:
   
  
Lloyd Paul Aiello, MD, PhD
 
Investigator Specifics:
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Member of Section:
Eye Research
Vascular Cell Biology

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Computer Resource

Current Fellows, Students, or Lab Members:
Manvi Prakash, MD
Yukio Sassa, PhD
Paolo Antonio Silva, RPh, MD

Past Fellows, etc.:
Fareed Ali
Mark Cahill
Joseph Coney
Gus Cordahi
Julie Dean
Stella Douros
Alejandro  Espaillat
Lucy Goddard
Marlyn Goldberg
Rama Jager
Miyuki Katai
David Rho
Susan Rook
Haytham Salti
Izumi Suzuma
Nigel Timothy
Edmund Wong
Jun Wong

Related Resources:
Section on Vascular Cell Biology
National Eye Institute
Beetham Eye Institute
Juvenile Diabetes Foundation
American Academy of Ophthalmology
National Eye Institute Trials
American Diabetes Association
Search the Medical Literature
BWH von Hippel-Lindau Disease (VHL) Program
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Section on Eye Research

 
 
Lloyd Paul Aiello, MD, PhD
Director: Beetham Eye Institute
Joslin Diabetes Center
Head: Eye Research
Joslin Diabetes Center
Associate Professor of Ophthalmology
Harvard Medical School
 
7/1/1992 -  
 
 Studies to eliminate visual loss from diabetic retinopathy and other ischemic retinopathies


Dr. Lloyd Paul Aiello is an Associate Professor of Ophthalmology at Harvard Medical School, Director of the William P. Beetham Eye Institute and Investigator and Section Head of the Section of Eye Research at the Joslin Diabetes Center. An ophthalmologist with retinal subspecialty training, Dr. Aiello focuses 80% of his time on scientific research, particularly aimed at determining the biochemisty and molecular mechanisms underlying retinal vascular disorders such as diabetic eye disease and vascular retinal tumors.

Dr, Aiello is also internationally recognized for his leadership roles in diabetic retinopathy clinical trial development and implementation, and he maintains 20% of his time in clinical ophthalmic care of diabetic eye disease and other retinal vascular disorders.

Dr Aiello and his co-workers are investigating the molecular mechanisms responsible for both early diabetic retinopathy and the more advanced complications of retinal diseases, including diseases of the macula in the eye. This information is used to determine potential therapeutic targets and then studies proceed to evaluation of the resulting new treatment approaches in animals and subsequent development and implementation of human clinical trials. These studies may help develop novel, non-invasive therapies providing new treatment options for diabetic retinopathy, diabetic macular edema and other ischemic retinal vascular disorders which currently account for the majority of blindness among working-age Americans.

Dr. Aiello's laboratory has significant research efforts focusing on understanding the expression, regulation, and signalling of vascular endothelial growth factor (VEGF) and its receptors. Dr. Aiello and Dr. King's laboratory reported several years ago that VEGF, a major growth factor which can be regulated by hypoxia, is elevated in the fluids of the eye (both vitreous and aqueous)in diabetic patients with proliferative retinopathy. The increased levels of VEGF are normalized when proliferative retinopathy is in remission due to either vitrectomy or laser photocoagulation of the retina. Dr. Aiello has extensively studied the regulation of the expression of VEGF and its receptors by hypoxia, high glucose, diabetes and other mediating factors such as bFGF. Studies have also determined the signaling mechanisms for VEGF in retinal cells. Recent research is determining the molecular mechanisms by which concomitant hypertension exacerbates diabetic retinopathy. In addition, Dr. Aiello's laboratory has been studying the expression of another growth factor called PEDF, which is also regulated by hypoxia, but unlike VEGF, PEDF is believed to inhibit the expansion and growth of endothelial cells.

These studies and extensive work done by their close collaborator Dr King, have led to the demonstration that the beta isoform of the enzyme Protein Kinase C mediates many of the detrimental changes of diabetes in the eye. A selective inhibitor of PKC-beta has been developed by Dr King which prevents many of the abnormal changes associated with diabetes both in cell culture and in animal models. This inhibitor, which is given orally, is now in phase 3 clinical trials to determine if it can delay or prevent the development of proliferative diabetic retinopathy or sight threatening diabetic macular edema. Dr. Aiello is the Chairman of three multicenter, multinational, randomized, placebo-controlled, double-masked clinical trials using this PKC-beta inhibitor.


Biographical Sketch:

Dr. Aiello is a graduate of the University of Pennsylvania and received his M.D. and Ph.D. (biochemistry) degrees from the Boston University School of Medicine. He completed his residency in ophthalmology at the Wilmer Ophthalmological Institute at Johns Hopkins University and Hospital before coming to the Joslin Diabetes Center. At the Joslin Diabetes Center he completed both a clinical vitreoretinal fellowship and a research fellowship before joining the Joslin staff in 1994.

Dr Aiello is an author of over 59 original scientific papers, and over 97 publications including scientific reviews, book chapters and symposium proceedings. In recognition of his achievements, Dr. Aiello has been awarded the Marios C. Balidimos, M.D. Award from the American Diabetes Association's Massachusetts Affiliate, the Dolly Green Scholarship from Research to Prevent Blindness, the Capps Scholarship in Diabetes from Harvard Medical School and the Alcon Award for outstanding contributions in the field of vision research from the Alcon Research Institute. He has been awarded several fellowships, including a Pfizer Postdoctoral Fellowship in Diabetes and Endocrinology and a Heed/Knapp Fellowship from The Heed Ophthalmic Foundation. Among his professional affiliations, Dr. Aiello holds membership in the American Diabetes Association, the Association for Research in Vision and Ophthalmology, the Macula Society, the Retina Society, the American Academy of Ophthalmology and the Massachusetts Medical Society.

Dr Aiello has participated in several grant review committees including serving as chair of the Complications Section of the Medical Science Review Committee of the Juvenile Diabetes Foundation International and Chair of the American Diabetes Association Lions SightFirst Diabetic Retinopathy Research Program review panel. Dr. Aiello is on the editorial board of the American Journal of Ophthalmology and RETINA.


Selected References (see Curriculum Vitae or Medline Listing):


Aiello, L.P., Avery, R.L., Arrigg, P.G., Keyt, B., Aiello, L.M., Jampel, H.D., Shah, S.T., Pasquale, L.R., Thieme, H., Iwamoto, M.A., Park, J.E., Nguyen, H.V., Ferrara, N., King, G.L., Vascular Endothelial Growth Factor in Ocular Fluids of Patients with Diabetic Retinopathy and Other Retinal Disorders, N Eng J Med., 1994, 331: 1480-1487.

Aiello, L.P., Pierce, E.A., Foley, E.D., Takagi, H., Chen, H., Riddle,
L., Ferrara, N., King, G.L., Smith, L.E.H., Inhibition of Vascular Endothelial Growth Factor Suppresses Retinal Neovascularization in Vivo, Proc. Natl.
Acad. Sci., USA, 1995, 92(23): 10457-10461.

Pu, X., Aiello, L.P., Ishii, H., Jiang, Z.Y., Park, D.J., Robinson, G.S.,
Takagi, H., Newsome, W.P., Jirousek, J, King, G.L., Characterization of Vascular Endothelial Growth Factor's Effect on the Activation of Protein Kinase C., Its Isoforms and Endothelial Cell Growth, J Clin Invest., 1996, 98(9): 2018-2026.

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. 1997; 46:1473-1480.

Aiello LP, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL, Klein R. Diabetic Retinopathy: Technical Review. American Diabetes Association. Diabetes Care. 1998; 21:143-156.

Aiello LP, Hata Y. Molecular Mechanisms of Growth Factor Action in Diabetic Retinopathy. Current Opinion Endocrinology and Diabetes. 1999; 6:146-156.

Suzuma I, Hata Y, Clermont A, Pokras F, Rook S, Suzuma K, Feener E, Aiello LP. Cyclic Stretch And Hypertension Induce Retinal Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2: Potential Mechanisms for Exacerbation of Diabetic Retinopathy by Hypertension. Diabetes. 2001;50:444-454.

Aiello LP, Cahill MT, Wong JS. Systemic Considerations in the Management of Diabetic Retinopathy. Am. J. Ophthalmol. 2001;132(5):760-76.

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. Ophthalmol. 2002; in press.

Suzuma I, Suzuma K, Ueki K, Hata Y, Feener EP, King GL, Aiello LP.Stretch-Induced Retinal VEGF Expression is Mediated by PI3 Kinase and PKC-Zeta but Not by Stretch-Induced ERK1/2, Akt, Ras or Classical/Novel PKC Pathways. J. Biol. Chem. 2002;277(2):1047-57.