ArticleExperimental eye research2014
Novel transgenic mouse models develop retinal changes associated with early diabetic retinopathy similar to those observed in rats with diabetes mellitus.
Article in Experimental eye research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
- Overexpression of D-amino acid oxidase prevents retinal neurovascular pathologies in diabetic rats.Diabetologia · 2021Article
- Assessment of Global and Local Alterations in Retinal Layer Thickness in Ins2 (Akita) Diabetic Mice by Spectral Domain Optical Coherence Tomography.Journal of ophthalmology · 2018Article
- Long non-coding RNA MEG3 mediates high glucose-induced endothelial cell dysfunction.International journal of clinical and experimental pathology · 2018Article
- Aldose reductase, ocular diabetic complications and the development of topical Kinostat(®).Progress in retinal and eye research · 2016Review
- Downregulation of the Canonical WNT Signaling Pathway by TGFβ1 Inhibits Photoreceptor Differentiation of Adult Human Müller Glia with Stem Cell Characteristics.Stem cells and development · 2016Article
- Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in retinal microglia.Investigative ophthalmology & visual science · 2014Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Retinal capillary pericyte degeneration has been linked to aldose reductase (AR) activity in diabetic retinopathy (DR). Since the development of DR in mice and rats has been reported to differ and that this may be linked to differences in retinal sorbitol levels, we have established new murine models of early onset diabetes mellitus as tools for investigating the role of AR in DR. Transgenic diabetic mouse models were developed by crossbreeding diabetic C57BL/6-Ins2(Akita)/J (AK) with transgenic C57BL mice expressing green fluorescent protein (GFP), human aldose reductase (hAR) or both in vascular tissues containing smooth muscle actin-α (SMAA). Changes in retinal sorbitol levels were determined by HPLC while changes of growth factors and signaling were investigated by Western Blots. Retinal vascular changes were quantitatively analyzed on elastase-digestion flat mounts. Results show that sorbitol levels were higher in neural retinas of diabetic AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors VEGF, IGF-1, bFGF and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK, and P-44/42 MAPK. Increased loss of nuclei per capillary length and a significant increase in the percentage of acellular capillaries presented in 18 week old AK-SMAA-GFP-hAR mice. These changes are similar to those observed in streptozotocin-induced diabetic rats. Retinal changes in both mice and rats were prevented by inhibition of AR. These studies confirm that the increased expression of AR in mice results in the development of retinal changes associated with the early stages of DR that are similar to those observed in rats.
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