Retina in a dish: Cell cultures, retinal explants and animal models for common diseases of the retina

Schnichels, Sven; Paquet-Durand, François; Löscher, Marina; Tsai, Teresa; Hurst, José; Joachim, Stephanie C.; Klettner, Alexa

doi:10.1016/j.preteyeres.2020.100880

Cited by 98 publications

(81 citation statements)

References 479 publications

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“…In contrast, in clinical trials investigators are able to control a part of participants' behaviour. Additionally, metabolism and aging of animals and supplemented doses of antioxidants differ from the human being context [10,11,61].…”

Section: Discussionmentioning

confidence: 99%

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Glaucoma and Antioxidants: Review and Update

et al. 2020

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Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to assemble the studies published in relation to antioxidant supplementation and its effects on glaucoma and to offer the reader an update on this field. With this purpose, we have included studies in animal models of glaucoma and clinical trials. Although there are variable results, supplementation with antioxidants in glaucoma may be a promising therapy in glaucoma.

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Section: Discussionmentioning

confidence: 99%

“…However, in this context other animal models have also been considered. Animal model of glaucoma have been extensively described elsewhere [10,11].…”

Section: Introductionmentioning

confidence: 99%

Glaucoma and Antioxidants: Review and Update

et al. 2020

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“…The presence of several cell types allows the study of in vivo dynamics of cell-cell interaction, immune responses, and degeneration pathways. Retinal explant models provide insights into retinal pathologies and can be used for therapy testing (Li et al, 2018;Cheng et al, 2019;Schnichels et al, 2020). However, their use in AMD research is still limited.…”

Section: Discussionmentioning

confidence: 99%

“…Especially designed growth medium, containing growth factors for neurons, supports cell survival. Co-cultivation with retinal pigment epithelium (RPE) cells improves tissue structure, cellular organization, and preservation of photoreceptors (Di Lauro et al, 2016;Schnichels et al, 2020). Zhao and Barnstable (Zhao and Barnstable, 1996) pointed out that retinoic acid but not basic fibroblast growth factor (bFGF) promotes rod photoreceptor differentiation, whereas bFGF endorses RGC differentiation in ex vivo rat retinae.…”

Section: Organ Cultures: Advantages and Challengesmentioning

confidence: 99%

“…The absence of a macula in these animals makes it even more difficult. Therefore, it can be concluded that all these models give only simplified information on the pathogenesis of this complex disease, as reviewed in detail in Schnichels et al (2020). Due to the lack of suitable ex vivo models for AMD, so far, most studies on primary RPE cultures have been performed (Schnichels et al, 2020).…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

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Organ Cultures for Retinal Diseases

et al. 2020

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The successful development of novel therapies is closely linked with understanding the underlying pathomechanisms of a disease. To do so, model systems that reflect human diseases and allow for the evaluation of new therapeutic approaches are needed. Yet, preclinical animal studies often have limited success in predicting human physiology, pathology, and therapeutic responses. Moreover, animal testing is facing increasing ethical and bureaucratic hurdles, while human cell cultures are limited in their ability to represent in vivo situations due to the lack of the tissue microenvironment, which may alter cellular responses. To overcome these struggles, organ cultures, especially those of complex organs such as the retina, can be used to study physiological reactions to substances or stressors. Human and animal organ cultures are now well established and recognized. This mini-review discusses how retinal organ cultures can be used to preserve tissue architecture more realistically and therefore better represent disease-related changes. It also shows how molecular biological, biochemical, and histological techniques can be combined to investigate how anatomical localization may alter cellular responses. Examples for the use of retinal organ cultures, including models to study age-related macular degeneration (AMD), retinitis pigmentosa (RP), central artery occlusion (CRAO), and glaucoma are presented, and their advantages and disadvantages are discussed. We conclude that organ cultures significantly improve our understanding of complex retinal diseases and may advance treatment testing without the need for animal testing.

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Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration

Keenan,

Bailey,

Abraham

et al. 2024

JAMA Ophthalmol

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ImportanceExisting therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable.ObjectiveTo evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD.Design, Setting, and ParticipantsThis was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023.InterventionAfter a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years.Main Outcomes and MeasuresThe primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase.ResultsOf the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was −0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, −0.4 to 0.9; P = .44) for visual acuity and 0.7 μm per month (−0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants).Conclusions and RelevanceIn this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

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Retina in a dish: Cell cultures, retinal explants and animal models for common diseases of the retina

Cited by 98 publications

References 479 publications

Glaucoma and Antioxidants: Review and Update

Glaucoma and Antioxidants: Review and Update

Organ Cultures for Retinal Diseases

Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration

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