Lipidmetabolism in retinal neovascular disease with emphasize on diabetic retinopathy and age related macular degeneration: role of polyunsuturated fatty acids (PUFA) as therapeutic intervention.
Final Report Abstract
The initial idea of the project was to explore the influence of metabolic dysregulation on the development of vasoproliferative retinal diseases with a specific focus on retinopathy of prematurity (ROP), age related macular degeneration (AMD) and diabetic retinopathy. We were able to show that omega 3 and 6 substituion through modified food intake was able to change the outcome in a model of AMD that is mainly triggered through inflammation. However through the course of my time in Boston we slowly progressed to see that humoral components such as platelets would play a major role in neovascularization. This is particularly interesting because the role of platelets in angiogenesis in general has already been studied to some extent but no research has been done in retinal diseases. If our hypothesis and the results that we have observed in our preclinical model are also seen in human beings, this could have a huge impact on the way premature infants are treated in our neonatal intensive care units. However, there have also been a number of projects that I have not been able to get any interesting results from. Acetylcholine receptors for example have been a target of several drugs and it has also been postulated that these drugs might have an influence on neovascularization. In our model however I did not observe any effect. Furthermore did we tried to treat mice with different noble gases (eg xenon) but could not go ahead with this project even though the idea would have been striking to treat premature babies with xenon to protect from developing ROP. This project however was not manageable due to the problem of xenon to be scarcely available.
Publications
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IGF-1 in retinopathy of prematurity, a CNS neurovascular disease. Early Hum Dev. 2016 Nov;102:13-19
Liegl R, Löfqvist C, Hellström A, Smith LE
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Retinopathy of prematurity: the need for prevention. Eye Brain. 2016 May 20;8:91-102
Liegl R, Hellström A, Smith LE
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Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice. Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):3862-3870
Fu Z, Liegl R, Wang Z, Gong Y, Liu CH, Sun Y, Cakir B, Burnim SB, Meng SS, Löfqvist C, SanGiovanni JP, Hellström A, Smith LEH
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FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice. Cell Rep. 2017 Feb 14;18(7):1606-1613
Fu Z, Gong Y, Liegl R, Wang Z, Liu CH, Meng SS, Burnim SB, Saba NJ, Fredrick TW, Morss PC, Hellstrom A, Talukdar S, Smith LE
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Sema3f Protects Against Subretinal Neovascularization In Vivo. EBioMedicine. 2017 Apr;18:281-287
Sun Y, Liegl R, Gong Y, Bühler A, Cakir B, Meng SS, Burnim SB, Liu CH, Reuer T, Zhang P, Walz JM, Ludwig F, Lange C, Agostini H, Böhringer D, Schlunck G, Smith LEH, Stahl A
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Photoreceptor glucose metabolism determines normal retinal vascular growth. EMBO Mol Med. 2018 Jan;10(1):76-90
Fu Z, Löfqvist CA, Liegl R, Wang Z, Sun Y, Gong Y, Liu CH, Meng SS, Burnim SB, Arellano I, Chouinard MT, Duran R, Poblete A, Cho SS, Akula JD, Kinter M, Ley D, Pupp IH, Talukdar S, Hellström A, Smith LE
