Experimental Models in Neovascular Age Related Macular Degeneration

Rastoin, Olivia; Pagès, Gilles; Dufies, Maeva

doi:10.3390/ijms21134627

Cited by 30 publications

(44 citation statements)

References 64 publications

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“…Furthermore, we confirmed the retinal protective ability of the RdECM using the Laser-CNV and the NMU-RD model due to their wide use as retinal degeneration models, including AMD and RP [ 55 , 56 , 57 , 58 ]. The RdECM-treated Laser-CNV mice showed similar wound recovery as the Avastin-treated mice, whereas the recovery was nearly unchanged in the collagen-treated mice.…”

Section: Discussionsupporting

confidence: 60%

Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology

et al. 2021

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Retinal degeneration is a leading cause of incurable vision loss and blindness. The increasing incidence of retinal degeneration has triggered research into the development of in vitro retinal models for drug development and retinal alternatives for transplantation. However, the complex retinal structure and the retinal microenvironment pose serious challenges. Although 3D cell printing technology has been widely used in tissue engineering, including in vitro model development and regeneration medicine, currently available bioinks are insufficient to recapitulate the complex extracellular matrix environment of the retina. Therefore, in this study, we developed a retinal decellularized extracellular matrix (RdECM) from the porcine retina and evaluated its characteristics. The RdECM conserved the ECM components from the native retina without cellular components. Then, we mixed the RdECM with collagen to form a bioink and confirmed its suitability for 3D cell printing. We further studied the effect of the RdECM bioink on the differentiation of Muller cells. The retinal protective effect of the RdECM bioink was confirmed through a retinal degeneration animal model. Thus, we believe that the RdECM bioink is a promising candidate for retinal tissue engineering.

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Section: Discussionsupporting

confidence: 60%

Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology

et al. 2021

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“…However, one distinct disadvantage of mice and rats is the lack of an anatomical macula. Using mouse models, researchers were able to recreate many of the AMD histological features such as the thickening of Bruch’s membrane, the accumulation of subretinal deposits as well as inflammatory cascade induction together with macrophages and microglia activation [ 38 , 39 ]. These features were obtained using gene therapies, but also laser-induction techniques and high-fat diets [ 40 ].…”

Section: Retinal Pathologies and In Vivo Modelsmentioning

confidence: 99%

Looking for In Vitro Models for Retinal Diseases

Alfonsetti

Castelli

Benedetti

et al. 2021

IJMS

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Retina is a layered structure of the eye, composed of different cellular components working together to produce a complex visual output. Because of its important role in visual function, retinal pathologies commonly represent the main causes of visual injury and blindness in the industrialized world. It is important to develop in vitro models of retinal diseases to use them in first screenings before translating in in vivo experiments and clinics. For this reason, it is important to develop bidimensional (2D) models that are more suitable for drug screening and toxicological studies and tridimensional (3D) models, which can replicate physiological conditions, for investigating pathological mechanisms leading to visual loss. This review provides an overview of the most common retinal diseases, relating to in vivo models, with a specific focus on alternative 2D and 3D in vitro models that can replicate the different cellular and matrix components of retinal layers, as well as injury insults that induce retinal disease and loss of the visual function.

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Section: Introductionmentioning

confidence: 99%

“…Laser-induced CNV has been utilized to develop the standard of care for CNV in humans, intravitreal injection of anti-VEGF antibodies, supporting its relevance to human disease [20,21]. In fact, the murine laser-induced CNV model is considered a standard pre-requisite for wet AMD clinical trials [22,23]. Laser-induced CNV has also been used to develop other clinically relevant therapeutic modalities, such as intravitreal injection of corticosteroids [24,25], which is particularly effective in treatment of VEGF non-responders [26,27].…”

Section: Introductionmentioning

confidence: 99%

“…Laser-induced CNV is a progressive model, proceeding through an initial angiogenic phase, which begins by day 3 post-laser photocoagulation, and peaks at day 7 post-photocoagulation [23]. Neovascular lesions begin to regress after day 7, and by day 28 post-laser photocoagulation, resolve nearly completely [22,23]. Contrastingly, in human wet AMD patients, AMD lesions remain stable over time, gradually growing if left untreated, and remaining static if treated with anti-VEGF therapy [2].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of sex differences in laser-induced choroidal neovascularization severity, phenotype and disease progression

Pearsall

2022

Preprint

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Age-related macular degeneration (AMD) progresses through two phases: a non-exudative “dry” stage that compromises vision but does not involve angiogenesis, and an angiogenic “wet” phase characterized by choroidal neovascularization (CNV), in which neovessels from the choroid break through the Bruch’s membrane to form neovascular lesions in the macula. If left untreated, CNV leads to permanent central blindness, which the current standard of care (anti-VEGF therapy) arrests but does not reverse. In laser-induced CNV, a laser is used to rupture the Bruch’s membrane, prompting the outgrowth of choroidal blood vessels in a wound healing response. This model was used to develop currently available CNV therapeutics, such as intravitreal injection of anti-VEGF and corticosteroid therapies and is considered a gold standard model for CNV. Laser-induced CNV thus remains a highly clinically relevant model of CNV secondary to AMD and other pathologies, such as myopia. A rapidly growing body of research suggests that the pathogenesis of myriad diseases is highly dependent on biological sex, yet most studies use only male animals. This highlights the importance of determining whether the severity and pathogenesis of commonly used models of disease, for example laser-induced CNV, differ between sexes. In the present study, we tracked longitudinal progression and pathogenesis of laser-induced CNV in male and female animals, and found that CNV severity did not differ between sexes. This lack of difference recapitulates findings in human patients with CNV, which have also identified that both sexes are at equal risk of CNV development in the contexts of both age-related macular degeneration induced CNV and myopic CNV.

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Experimental Models in Neovascular Age Related Macular Degeneration

Cited by 30 publications

References 64 publications

Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology

Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology

Looking for In Vitro Models for Retinal Diseases

Evaluation of sex differences in laser-induced choroidal neovascularization severity, phenotype and disease progression

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