Mouse microphthalmia‐associated transcription factor (<i>Mitf</i>) mutations affect the structure of the retinal vasculature

Daníelsson, Stefán Broddi; García‐Llorca, Andrea; Reynisson, Hallur; Eysteinsson, Þór

doi:10.1111/aos.15140

Cited by 4 publications

(5 citation statements)

References 55 publications

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“… 34 – 38 One gene of particular interest, Mitf , is expressed solely in the RPE and plays a crucial role in RPE function. 39 – 42 Loss of this gene has been connected to the loss of RPE pigmentation and the loss of RPE phenotype, thus supporting the results seen from H&E staining and TEM. 43 , 44 RT-qPCR also showed Mitf gene expression in 12 month p;d LCHADD RPE/sclera was 60% lower compared to WT, confirming RNA-sequencing results ( Fig.…”

Section: Resultssupporting

confidence: 73%

“…The downregulation of Mitf further supports RPE dysfunction and loss of boundary formation as this gene has been shown to be crucial in RPE development and differentiation and transepithelial transport. 41,42 Overall, the LCHADD mouse chorioretinopathy mirrors what has been observed in patients with LCHADD and provides a useful model to study the molecular mechanisms involved with the chorioretinopathy.…”

Section: Discussionmentioning

confidence: 77%

“…54,55 Whereas we report here that LCHADD mice have increased vacuoles in the choroid and many DEGs in LCHADD mice have been reported to play a role in angiogenesis and vasculature, the quality of the choroid was outside of the scope of this paper. [34][35][36][37][38]42 Therefore, it will be important to use appropriate techniques, such as OCT angiography, to assess the vasculature of this LCHADD mouse.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients

Babcock,

Curtis,

Gaston

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Section: Resultssupporting

confidence: 73%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients

Babcock,

Curtis,

Gaston

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…The retinal circulation is a true end artery system, with all the blood from the retinal arteries passing via the capillary beds to retinal venules and the central retinal vein. With fundus imaging, the retinal circulation can be easily viewed and examined, and structural and functional parameters such as vessel diameter ( Pedersen et al, 2005 ; Daníelsson et al, 2022 ; García-Llorca et al, 2023 ) and alterations in blood flow ( Marino et al, 2021 ) can be readily measured. The retinal vasculature tends to maintain a steady level of blood flow and oxygenation in the retina, by intrinsic autoregulation ( Riva et al, 1981 ; Dumskyj et al, 1996 ) in response to changes in perfusion pressure, intraocular pressure, or blood gasses (la Cour et al, 2000 ), but the myogenic response, considered to be the basis of autoregulation, is held to be intrinsic to vascular smooth muscle cells ( Davis and Hill, 1999 ).…”

Section: Carbonic Anhydrase and The Retinal Vasculaturementioning

confidence: 99%

Carbonic anhydrase, its inhibitors and vascular function

García-Llorca,

Carta,

Supuran

et al. 2024

Front. Mol. Biosci.

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It has been known for some time that Carbonic Anhydrase (CA, EC 4.2.1.1) plays a complex role in vascular function, and in the regulation of vascular tone. Clinically employed CA inhibitors (CAIs) are used primarily to lower intraocular pressure in glaucoma, and also to affect retinal blood flow and oxygen saturation. CAIs have been shown to dilate vessels and increase blood flow in both the cerebral and ocular vasculature. Similar effects of CAIs on vascular function have been observed in the liver, brain and kidney, while vessels in abdominal muscle and the stomach are unaffected. Most of the studies on the vascular effects of CAIs have been focused on the cerebral and ocular vasculatures, and in particular the retinal vasculature, where vasodilation of its vessels, after intravenous infusion of sulfonamide-based CAIs can be easily observed and measured from the fundus of the eye. The mechanism by which CAIs exert their effects on the vasculature is still unclear, but the classic sulfonamide-based inhibitors have been found to directly dilate isolated vessel segments when applied to the extracellular fluid. Modification of the structure of CAI compounds affects their efficacy and potency as vasodilators. CAIs of the coumarin type, which generally are less effective in inhibiting the catalytically dominant isoform hCA II and unable to accept NO, have comparable vasodilatory effects as the primary sulfonamides on pre-contracted retinal arteriolar vessel segments, providing insights into which CA isoforms are involved. Alterations of the lipophilicity of CAI compounds affect their potency as vasodilators, and CAIs that are membrane impermeant do not act as vasodilators of isolated vessel segments. Experiments with CAIs, that shed light on the role of CA in the regulation of vascular tone of vessels, will be discussed in this review. The role of CA in vascular function will be discussed, with specific emphasis on findings with the effects of CA inhibitors (CAI).

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“…Mitf -deficient mice show pathological features of albinism, microphthalmia, deafness, hypopigmentation, and retinal degeneration [21,23,25,34]. Recently, it was demonstrated that Mitf mutant and control mice have considerably different retinal vessel diameters and differences in the number of retinal vessels [35]. Loss of pigmentation, smaller eyes, failure of secondary bone resorption, fewer mast cells, and early-onset hearing loss are all or part of the abnormalities present in mice with mutations at the microphthalmia (mi) locus [34,[36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Progressive Cone-Rod Dystrophy and RPE Dysfunction in Mitfmi/+ Mice

García‐Llorca

Ólafsson

Sigurdsson

et al. 2023

Genes

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Mutations in the mouse microphthalmia-associated transcription factor (Mitf) gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to hypopigmentation, microphthalmia, deafness, and blindness. For instance, an association has been established between loss-of-function mutations in the mouse Mitf gene and a variety of human retinal diseases, including Waardenburg type 2 and Tietz syndromes. Although there is evidence showing that mice with the homozygous Mitfmi mutation manifest microphthalmia and osteopetrosis, there are limited or no data on the effects of the heterozygous condition in the eye. Mitf mice can therefore be regarded as an important model system for the study of human disease. Thus, we characterized Mitfmi/+ mice at 1, 3, 12, and 18 months old in comparison with age-matched wild-type mice. The light- and dark-adapted electroretinogram (ERG) recordings showed progressive cone-rod dystrophy in Mitfmi/+ mice. The RPE response was reduced in the mutant in all age groups studied. Progressive loss of pigmentation was found in Mitfmi/+ mice. Histological retinal sections revealed evidence of retinal degeneration in Mitfmi/+ mice at older ages. For the first time, we report a mouse model of progressive cone-rod dystrophy and RPE dysfunction with a mutation in the Mitf gene.

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Mouse microphthalmia‐associated transcription factor (Mitf) mutations affect the structure of the retinal vasculature

Cited by 4 publications

References 55 publications

The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients

The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients

Carbonic anhydrase, its inhibitors and vascular function

Progressive Cone-Rod Dystrophy and RPE Dysfunction in Mitfmi/+ Mice

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