Regenerative medicine in Fuchs' endothelial corneal dystrophy

Yuan, Amy; Pineda, Roberto

doi:10.4103/tjo.tjo_23_20

Cited by 4 publications

(3 citation statements)

References 63 publications

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“…When checking the survival of transplanted cells at 36 months, we found the peripheral scraped area was covered with only monkey cells, the middle area was mixed with both monkey and transplanted human cells, and the central area was covered with only transplanted human cells. These findings support that the transplanted cells actually stimulate the limited regeneration of monkey resident cells, similar to a previous description of descemetorhexis without endothelial keratoplasty in human ( 47 – 49 ). However, the long-term corneal recovery predominantly relies on the replacing function of transplanted human cells, which was different from the dependence of stimulated endothelial regeneration in rabbits.…”

Section: Discussionsupporting

confidence: 91%

Long-term corneal recovery by simultaneous delivery of hPSC-derived corneal endothelial precursors and nicotinamide

Li¹,

Jia²,

Zhao³

et al. 2022

Journal of Clinical Investigation

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Human pluripotent stem cells (hPSCs) hold great promise for the treatment of various human diseases. However, their therapeutic benefits and mechanisms for treating corneal endothelial dysfunction remain undefined. Here, we developed a therapeutic regimen consisting of the combination of hPSC-derived corneal endothelial precursors (CEPs) with nicotinamide (NAM) for effective treatment of corneal endothelial dysfunction. In rabbit and nonhuman primate models, intracameral injection of CEPs and NAM achieved long-term recovery of corneal clarity and thickness, similar with the therapeutic outcome of cultured human corneal endothelial cells (CECs). The transplanted human CEPs exhibited structural and functional integration with host resident CECs. However, the long-term recovery relied on the stimulation of endogenous endothelial regeneration in rabbits, but predominantly on the replacing function of transplanted cells during the 3-year follow-up in nonhuman primates, which resemble human corneal endothelium with limited regenerative capacity. Mechanistically, NAM ensured in vivo proper maturation of transplanted CEPs into functional CECs by preventing premature senescence and endothelial-mesenchymal transition within the TGF-β–enriched aqueous humor. Together, we provide compelling experimental evidence and mechanistic insights of simultaneous delivery of CEPs and NAM as a potential approach for treating corneal endothelial dysfunction.

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Section: Discussionsupporting

confidence: 91%

Long-term corneal recovery by simultaneous delivery of hPSC-derived corneal endothelial precursors and nicotinamide

Li¹,

Jia²,

Zhao³

et al. 2022

Journal of Clinical Investigation

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“…Furthermore, these advances could be instrumental in tracking the effects of novel therapeutics for FECD that may emerge in the near future. [33][34][35]…”

Section: Discussionmentioning

confidence: 99%

Assessing Fuchs Corneal Endothelial Dystrophy Using Artificial Intelligence–Derived Morphometric Parameters From Specular Microscopy Images

Prada,

Quintero,

Mendoza

et al. 2024

Cornea

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Purpose: The aim of this study was to evaluate the efficacy of artificial intelligence–derived morphometric parameters in characterizing Fuchs corneal endothelial dystrophy (FECD) from specular microscopy images. Methods: This cross-sectional study recruited patients diagnosed with FECD, who underwent ophthalmologic evaluations, including slit-lamp examinations and corneal endothelial assessments using specular microscopy. The modified Krachmer grading scale was used for clinical FECD classification. The images were processed using a convolutional neural network for segmentation and morphometric parameter estimation, including effective endothelial cell density, guttae area ratio, coefficient of variation of size, and hexagonality. A mixed-effects model was used to assess relationships between the FECD clinical classification and measured parameters. Results: Of 52 patients (104 eyes) recruited, 76 eyes were analyzed because of the exclusion of 26 eyes for poor quality retroillumination photographs. The study revealed significant discrepancies between artificial intelligence–based and built-in microscope software cell density measurements (1322 ± 489 cells/mm2 vs. 2216 ± 509 cells/mm2, P < 0.001). In the central region, guttae area ratio showed the strongest correlation with modified Krachmer grades (0.60, P < 0.001). In peripheral areas, only guttae area ratio in the inferior region exhibited a marginally significant positive correlation (0.29, P < 0.05). Conclusions: This study confirms the utility of CNNs for precise FECD evaluation through specular microscopy. Guttae area ratio emerges as a compelling morphometric parameter aligning closely with modified Krachmer clinical grading. These findings set the stage for future large-scale studies, with potential applications in the assessment of irreversible corneal edema risk after phacoemulsification in FECD patients, as well as in monitoring novel FECD therapies.

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“…ROCK inhibitors are initially used to treat glaucoma, but their ability to increase adhesion, promote proliferation, and inhibit apoptosis of corneal endothelial cells have been demonstrated, making them potential treatments for other corneal endothelial disorders. [ 84 85 ] Clinical trials have been carried out to assess the potential benefits of adding ripasudil (Kowa Company Ltd, Nagoya, Japan), a ROCK inhibitor, to postoperative treatment since ripasudil was believed to accelerate postsurgical endothelial cell healing and elimination of corneal edema. However, the results of these trials are not available.…”

Section: Clinical Trialsmentioning

confidence: 99%

Therapeutic future of Fuchs endothelial corneal dystrophy: An ongoing way to explore

Liu,

Chiang,

Hung

et al. 2024

Taiwan Journal of Ophthalmology

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Fuchs endothelial corneal dystrophy (FECD) is one of the most common corneal diseases that causes loss of visual acuity in the world. FECD is a genetically and pathogenetically heterogeneous disease that results in the failure of corneal endothelial cells to maintain fluid balance and functional homeostasis of the cornea. Corneal edema, central guttae formation, and bullae development are common corneal pathologies. Currently, the mainstay of FECD treatment is surgery. However, limited sources of corneal graft and postsurgical complications remain problematic. In recent years, with advances in medical science and technology, there have been a few promising trials of new treatment modalities for FECD. In addition to new surgical methods, novel modalities can be classified into pharmacological-associated treatment, cell therapy-associated treatment, and gene therapy-associated treatment. In this article, our primary focus is on the most recent clinical trials related to FECD, and we present a stepwise approach to enhance FECD management and ultimately improve patient outcomes. We thoroughly searched for FECD clinical trials and reviewed the study designs, methodologies, and outcomes of each trial conducted within the past decade. It is imperative for physicians to stay up-to-date with these cutting-edge treatment approaches.

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Regenerative medicine in Fuchs' endothelial corneal dystrophy

Cited by 4 publications

References 63 publications

Long-term corneal recovery by simultaneous delivery of hPSC-derived corneal endothelial precursors and nicotinamide

Long-term corneal recovery by simultaneous delivery of hPSC-derived corneal endothelial precursors and nicotinamide

Assessing Fuchs Corneal Endothelial Dystrophy Using Artificial Intelligence–Derived Morphometric Parameters From Specular Microscopy Images

Therapeutic future of Fuchs endothelial corneal dystrophy: An ongoing way to explore

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