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Dyslipidemia and Diabetic Retinopathy

Award Number: R01EY016077
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2005
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Dyslipidemia and Diabetic Retinopathy - Recent advances using pharmacotherapy greatly expand treatment options for diabetic retinopathy. Intravitreal anti-VEGF immunotherapy has proven to be effective in resolving both neovascular diabetic retinopathy (DR) and diabetic macular edema (DME)(1-5). Large clinical studies, however, reveal that about 40% of patients do not respond to anti-VEGF therapy(1-3) and the withdrawal of anti-VEGF after the long-term use can lead to rebound effects with worsening of the symptoms. Importantly, anti-VEGF treatments are directed at the very late stage in the disease, when full reversal of retinal damage is difficult. Thus, a conceptual and technical breakthrough to identify novel targets and a strategy to cure this complication is paramount. Unique metabolic demands and highly specialized structure and function of the retina dictate complex regulatory pathways to support retinal metabolism while preserving autonomy behind the blood-retinal barrier (BRB)(6). This intricate balance is lost in a diabetic environment(7-9). An important example of such dysregulation is the shift in the dial of sphingolipid rheostat from protective, pro-barrier very long chain (VLC) ceramides (C≥26) to pro-inflammatory and pro-apoptotic Short Chain (SC) ceramides (C≤24). SC ceramides in the retina are mainly produced from sphingomyelins by acid sphingomyelinase (ASM) (10-14). Production of VLC ceramides involves Elongation of very long chain fatty acids protein 4 (ELOVL4)-mediated synthesis of VLC saturated fatty acids that are then incorporated into ceramides by the action of ceramide synthases (CerS)(15). We have previously demonstrated that ASM is highly upregulated(10) and ELOVL4 is downregulated(19) in the diabetic retina. Downregulation of ASM or upregulation of ELOVL4 were protective against diabetes-induced retinal vascular degeneration in cell culture and animal models(10, 20). We hypothesize that the shift in the ceramide rheostat dial from SC to VLC ceramides will improve the outcome of diabetic retinopathy by: 1) preventing SC ceramide-mediated pro-inflammatory and pro-apoptotic changes while 2) maintaining VLC-ceramide barrier function.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $390,876 )
2025	2025	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Vision Research	001	17	7/30/2025	NON-COMPETING CONTINUATION	$390,876
2025	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	15	2/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $390,876

Issue Date FY: 2024 ( Subtotal = $390,876 )
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Vision Research	001	16	8/19/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$390,876
2024	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	15	8/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $390,876

Issue Date FY: 2023 ( Subtotal = $390,876 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	15	6/5/2023	NON-COMPETING CONTINUATION	$390,876
														Subtotal = $390,876

Issue Date FY: 2022 ( Subtotal = $379,150 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	14	7/5/2022	NON-COMPETING CONTINUATION	$379,150
														Subtotal = $379,150

Issue Date FY: 2021 ( Subtotal = $405,001 )
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	13	8/31/2021	COMPETING CONTINUATION	$405,001
2021	2020	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	12	5/3/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $405,001

Issue Date FY: 2020 ( Subtotal = $373,053 )
2020	2020	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	12	12/9/2019	NON-COMPETING CONTINUATION	$335,747
2020	2020	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	12	1/28/2020	NON-COMPETING CONTINUATION	$37,306
														Subtotal = $373,053

Issue Date FY: 2019 ( Subtotal = $373,512 )
2019	2019	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	11	12/3/2018	NON-COMPETING CONTINUATION	$373,512
														Subtotal = $373,512

Issue Date FY: 2018 ( Subtotal = $373,954 )
2018	2018	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	10	11/22/2017	NON-COMPETING CONTINUATION	$336,558
2018	2018	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	10	5/24/2018	NON-COMPETING CONTINUATION	$37,396
														Subtotal = $373,954

Issue Date FY: 2017 ( Subtotal = $374,379 )
2017	2017	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	9	6/28/2017	NON-COMPETING CONTINUATION	$37,438
2017	2017	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	9	12/12/2016	NON-COMPETING CONTINUATION	$336,941
														Subtotal = $374,379

Issue Date FY: 2016 ( Subtotal = $388,163 )
2016	2016	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	8	12/1/2015	COMPETING CONTINUATION	$388,163
														Subtotal = $388,163

Issue Date FY: 2014 ( Subtotal = $364,415 )
2014	2014	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	7	11/22/2013	NON-COMPETING CONTINUATION	$334,667
2014	2014	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	7	4/16/2014	NON-COMPETING CONTINUATION	$29,748
														Subtotal = $364,415

Issue Date FY: 2013 ( Subtotal = $353,651 )
2013	2013	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	6	5/21/2013	NON-COMPETING CONTINUATION	$18,613
2013	2013	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	6	11/20/2012	NON-COMPETING CONTINUATION	$335,038
														Subtotal = $353,651

Issue Date FY: 2012 ( Subtotal = $372,654 )
2012	2012	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	001	5	3/1/2012	NON-COMPETING CONTINUATION	$37,266
2012	2012	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	5	11/10/2011	NON-COMPETING CONTINUATION	$335,388
														Subtotal = $372,654

Issue Date FY: 2011 ( Subtotal = $386,023 )
2011	2011	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	4	11/19/2010	COMPETING CONTINUATION	$386,023
														Subtotal = $386,023

Issue Date FY: 2007 ( Subtotal = $318,137 )
2007	2007	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	3	7/19/2007	NON-COMPETING CONTINUATION	$318,137
														Subtotal = $318,137

Issue Date FY: 2006 ( Subtotal = $325,576 )
2006	2006	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	2	8/1/2006	NON-COMPETING CONTINUATION	$325,576
														Subtotal = $325,576

Issue Date FY: 2005 ( Subtotal = $348,347 )
2005	2005	MICHIGAN STATE UNIVERSITY	301 ADMINISTRATION BLDG	EAST LANSING	MI	48824	INGHAM	USA	Vision Research	000	1	8/1/2005	NEW	$348,347
														Subtotal = $348,347

Grand Total All Awards = $6,308,643

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Dyslipidemia and Diabetic Retinopathy

Award Number: R01EY016077

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2005

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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