Feasibility of cell-based therapy combined with descemetorhexis for treating Fuchs endothelial corneal dystrophy in rabbit model

Abstract

Corneal transparency is maintained by the corneal endothelium through its pump and barrier function. Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet’s membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet’s membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet’s membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet’s membrane removal) and on the intact peripheral Descemet’s membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet’s membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet’s membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet’s membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.

Long-term observation and sequencing analysis of SKPs-derived corneal endothelial cell-like cells for treating corneal endothelial dysfunction

“…Although Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasties (DMEK) are now the most commonly used surgical method of endothelial keratoplasty [25][26][27], the anterior chamber injection method may be a very promising method to be clinically used. Recently, Okumura reported serial studies showing that injection of cultivated corneal endothelial cells with Rock inhibitor (Y-27632) into rabbit or monkey anterior chambers could exert good therapeutic effect for corneal endothelial dysfunction [28][29][30][31]. The Y-27632 could signi cantly promote cell adhesion and proliferation, and inhibit apoptosis of corneal endothelial cells [32].…”

Trends in corneal transplantation at the University Eye Hospital in Tübingen, Germany over the last 12 years: 2004 – 2015

“…Potential future alternatives to EK that could help address the not fulfilled demand for donor corneas and reduce the growing waiting list include removing central guttae and regenerating a central endothelial cell layer from healthy peripheral cells in patients with Fuchs' dystrophy [ 37 ] or injecting cultured human corneal endothelial cells into the anterior chamber to rehabilitate corneas without residual healthy endothelium and recover of the corneal transparency [ 38 , 39 ].…”

Quantification of the Posterior Cornea Using Swept Source Optical Coherence Tomography

“…An analogous situation exists with therapeutic HCEnC injection, which will require removal of central endothelium using a scraping technique to make room on the host DM for injected cells. 21 Studies of cell injection in felines have shown that scraping a larger segment of host endothelium is correlated with significantly worse outcomes, while eyes with smaller scraped areas demonstrated recovery even without injection of cells. 37 Similar to DMET/DWEK/DMT, eyes with a larger EAL may possess more HCEnCs capable of stimulating regeneration at the edges of the scraped endothelial wound; therefore, host EAL may influence the optimal amount of endothelium to be removed.…”

“… 18 – 20 A portion of the host endothelium must be cleared before injection to facilitate attachment of injected cells to the native DM, and determination of the amount of endothelium to be removed will require knowledge of the endothelium/DM size. 12 , 21 As such, it would be beneficial to identify an accurate in vivo measurement parameter of the host endothelium/DM complex. Furthermore, to this point the TZ has been characterized only in vitro, via scanning electron microscopy (SEM) 22 or immunostaining.…”