Charles Alpers

Personal Information
Title Professor
Expertise Nephropathy
Institution University of Washington
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Data Summary
Grants/SubContracts 1
Progress Reports 1
Publications 13
Protocols 0
Committees 2

Characterization of a new model of diabetic retinopathy
Diabetic retinopathy (DR) is a major, common, and specific manifestation of diabetes, that has been estimated to be present in 86% of T1D patients. Approximately half of affected patients (42% off all T1D patients), will have vision-threatening retinopathy. The lack of a good model of this microvascular complication has hampered development and testing of effective therapeutics for DR. We present exciting preliminary data that the BTBR ob/ob murine model of Type II diabetes may develop a proliferative microvascular retinopathy, concurrently with other retinal and microvascular complications of diabetes. The development of diabetes and diabetic complications in this model is the consequence of a genetic mutation resulting in leptin deficiency. Leptin replacement in these mice has been demonstrated by us to effect the reversal of diabetes and, in the case of the kidney, reverse the functional and structural manifestations of advanced diabetic nephropathy. Whether such a dramatic reversal of DR can also be achieved is unknown. We have been exploring the possibility of adapting a new imaging technology (OMAG) for studies of diabetic complications of microvascular origin that can allow investigators to follow the development of DR lesions sequentially over time in the living mouse. Building on these advances in diabetic model development, we propose the following specific aims: Specific Aim #1: To characterize a new mouse model of diabetic retinopathy (DR) and to test the potential for reversal of DR by maneuvers previously shown to reverse diabetic nephropathy in the BTBR ob/ob mouse model of Type 2 Diabetes.Specific Aim #2: to establish a new and non-invasive imaging approach for monitoring and quantitating the development of DR and its potential reversal in the live animal setting, that is directly relevant to the management of humans with DR or at risk to develop DR. Establishing a robust model of DR will enable us and others to better test therapies of potential benefit to humans with DR or at risk for DR in a preclinical setting, and will enable focused studies of the pathogenesis of DR and identify pathophysiologic pathways that result in progression or regression of this lesion.

Progress Reports
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Characterization of a new model of diabetic retinopathy (Alpers, Charles)
10/30/2013View Progress Report Document

Annual Reports
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Year: 2021; Items: 1

Reversal of hypertriglyceridemia in diabetic BTBR ob/ob mice does not prevent nephropathy.
Attie AD, Schueler KM, Keller MP, Mitok KA, Simonett SP, Hudkins KL, Mehrotra K, Graham MJ, Lee RG, Alpers CE
Laboratory investigation; a journal of technical methods and pathology, 2021

Year: 2018; Items: 2

A Novel Type 2 Diabetes Mouse Model of Combined Diabetic Kidney Disease and Atherosclerosis.
Bornfeldt KE, Kramer F, Batorsky A, Choi J, Hudkins KL, Tontonoz P, Alpers CE, Kanter JE
The American journal of pathology, 2018 (188), 343 - 352
Volumetric, Nanoscale Optical Imaging of Mouse and Human Kidney via Expansion Microscopy.
Chozinski TJ, Mao C, Halpern AR, Pippin JW, Shankland SJ, Alpers CE, Najafian B, Vaughan JC
Scientific reports, 2018 (8), 10396

Year: 2015; Items: 2

Serum amyloid A and inflammation in diabetic kidney disease and podocytes.
Anderberg RJ, Meek RL, Hudkins KL, Cooney SK, Alpers CE, Leboeuf RC, Tuttle KR
Laboratory investigation; a journal of technical methods and pathology, 2015 (95), 250 - 262
Submitted Externally
Interstitial eosinophilic aggregates in diabetic nephropathy: allergy or not?
Dai DF, Sasaki K, Lin MY, Smith KD, Nicosia RF, Alpers CE, Najafian B
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015
Submitted Externally

Year: 2014; Items: 2

Noninvasive imaging of retinal morphology and microvasculature in obese mice using optical coherence tomography and optical microangiography.
Zhi Z, Chao JR, Wietecha T, Hudkins KL, Alpers CE, Wang RK
Investigative ophthalmology & visual science, 2014 (55), 1024 - 30
Glomerular Disease: Looking beyond Pathology.
Wiggins RC, Alpers CE, Holzman LB, He JC, Salant DJ, Chugh SS, Natarajan R, Trachtman H, Brasile L, Star RA, Rys-Sikora KE, Moxey-Mims MM, Flessner MF
Clinical journal of the American Society of Nephrology : CJASN, 2014 (9), 1138 - 1140
Submitted Externally

Year: 2013; Items: 4

New targets for treatment of diabetic nephropathy: what we have learned from animal models.
Brosius FC, Alpers CE
Current opinion in nephrology and hypertension, 2013 (22), 17 - 25
Glomerular cell death and inflammation with high-protein diet and diabetes.
Meek RL, LeBoeuf RC, Saha SA, Alpers CE, Hudkins KL, Cooney SK, Anderberg RJ, Tuttle KR
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013 (28), 1711 - 1720
Submitted Externally
Reversibility of structural and functional damage in a model of advanced diabetic nephropathy.
Pichaiwong W, Hudkins KL, Wietecha T, Nguyen TQ, Tachaudomdach C, Li W, Askari B, Kobayashi T, O'Brien KD, Pippin JW, Shankland SJ, Alpers CE
Journal of the American Society of Nephrology : JASN, 2013 (24), 1088 - 1102
Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic db/db mice.
Reddy MA, Sumanth P, Lanting L, Yuan H, Wang M, Mar D, Alpers CE, Bomsztyk K, Natarajan R
Kidney international, 2013 (85), 362 - 373
Submitted Externally

Year: 2011; Items: 1

Mouse models of diabetic nephropathy.
Alpers CE, Hudkins KL
Current opinion in nephrology and hypertension, 2011 (20), 278 - 284

Year: 2010; Items: 1

BTBR Ob/Ob mutant mice model progressive diabetic nephropathy.
Hudkins KL, Pichaiwong W, Wietecha T, Kowalewska J, Banas MC, Spencer MW, Mühlfeld A, Koelling M, Pippin JW, Shankland SJ, Askari B, Rabaglia ME, Keller MP, Attie AD, Alpers CE
Journal of the American Society of Nephrology : JASN, 2010 (21), 1533 - 1542
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