From hair to cornea: toward the therapeutic use of hair follicle-derived stem cells in the treatment of limbal stem cell deficiency.

Limbal stem cell deficiency (LSCD) leads to severe ocular surface abnormalities that can result in the loss of vision. The most successful therapy currently being used is transplantation of limbal epithelial cell sheets cultivated from a limbal biopsy obtained from the patient's healthy, contralateral eye or cadaveric tissue. In this study, we investigated the therapeutic potential of murine vibrissae hair follicle bulge-derived stem cells (HFSCs) as an autologous stem cell (SC) source for ocular surface reconstruction in patients bilaterally affected by LSCD. This study is an expansion of our previously published work showing transdifferentiation of HFSCs into cells of a corneal epithelial phenotype in an in vitro system. In this study, we used a transgenic mouse model, K12(rtTA/rtTA) /tetO-cre/ROSA(mTmG) , which allows for HFSCs to change color, from red to green, once differentiation to corneal epithelial cells occurs and Krt12, the corneal epithelial-specific differentiation marker, is expressed. HFSCs were isolated from transgenic mice, amplified by clonal expansion on a 3T3 feeder layer, and transplanted on a fibrin carrier to the eye of LSCD wild-type mice (n = 31). The HFSC transplant was able to reconstruct the ocular surface in 80% of the transplanted animals; differentiating into cells with a corneal epithelial phenotype, expressing Krt12, and repopulating the corneal SC pool while suppressing vascularization and conjunctival ingrowth. These data highlight the therapeutic properties of using HFSC to treat LSCD in a mouse model while demonstrating a strong translational potential and points to the niche as a key factor for determining stem cell differentiation.

A case report of a patient with Pfeiffer syndrome, an FGRF 2 mutation (Trp290Cys) and unique ocular anterior segment findings.

PURPOSE: To report a case of a child with Pfeiffer syndrome, unique ocular anterior segment findings and a mutation in FGFR2 (Trp290Cys). METHODS: Case Report. RESULTS: We describe a patient with Pfeiffer syndrome with a unique constellation of ocular anterior segment anomalies including microcornea, limbal scleralization, corectopia and glaucoma. Genomic DNA extraction was heterozygous for a G to T mutation at nucleotide 870 of the fibroblast growth factor receptor 2 gene (FGFR2) which changes tryptophan (TGG) to cysteine (TGT) at amino acid position 290 (Trp290Cys). CONCLUSION: This case supports the association between Pfeiffer syndrome and severe ocular anterior segment anomalies, including glaucoma, and underscores the possible role that FGFR2 has in development of the anterior segment of the eye.

Capillary haemangiomas in association with morning glory disc anomaly.

PURPOSE AND METHOD: Capillary haemangiomas in children are usually isolated, but may have systemic associations. This accords with our finding of ocular malformations, especially "morning glory disc anomaly" (MGDA), in three children which are described. RESULTS: All three children had extensive capillary haemangiomas in combination with MGDA in one eye. One of the children also had microphthalmos in one eye and a partial agenesis of the corpus callosum. Another child had sclerocornea in one eye and congenital heart defects. CONCLUSION: An association of extensive capillary haemangiomas with MGDA is described. The embryological timing of such defects as well as investigation of the children is discussed. Extensive haemangiomas have not previously, to our knowledge, been described in association with MGDA.