scheffer c g Tseng

PURPOSE: Human corneal endothelial cells (HCECs) play a significant role in maintaining visual function. However, these cells are notorious for their limited proliferative capacity in vivo. Current treatment of corneal endothelial dysfunction resorts to corneal transplantation. Herein we describe an ex vivo engineering method to manufacture HCEC grafts suitable for transplantation through reprogramming into neural crest progenitors. METHODS: HCECs were isolated by collagenase A from stripped Descemet membrane of cadaveric corneoscleral rims, and induced reprogramming via knockdown with p120 and Kaiso siRNAs on collagen IV-coated atelocollagen...

PURPOSE: To assess the extent of inferior fornix shortening in conjunctivochalasis (CCh) and to evaluate whether fornix deepening reconstruction can restore the fornix tear reservoir in patients with CCh. MATERIALS AND METHODS: This was a retrospective review of five patients (3 unilateral and 2 bilateral eyes, total 7 eyes) with CCh who underwent fornix deepening reconstruction with conjunctival recession and amniotic membrane transplantation. Postsurgical outcome measures included changes in fornix depth with correlation to basal tear volumes, symptoms, corneal staining, and conjunctival inflammation...

No abstract text is available yet for this article.

The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregulated by dexamethasone. Continuous passage of these cells on 2D Matrigel resulted in a gradual loss of expression of these markers. However, such a loss was restored by seeding cells in 3D Matrigel where expression of TM markers was further upregulated upon continuous passage...

Quiescence and self-renewal of human corneal epithelial progenitor/stem cells (LEPC) are regulated by the limbal niche, presumably through close interaction with limbal (stromal) niche cells (LNC). Paired box homeotic gene 6 (Pax6), a conserved transcription factor essential for eye development, is essential for proper differentiation of limbal and corneal epithelial stem cells. Pax6 haploinsufficiency causes limbal stem cell deficiency, which leads to subsequent corneal blindness. We previously reported that serial passage of nuclear Pax6+ LNC resulted in the gradual loss of nuclear Pax6+ and neural crest progenitor status, the latter of which was reverted upon recovery of Pax6...

Homeostasis of the corneal epithelium is ultimately maintained by stem cells that reside in a specialized microenvironment within the corneal limbus termed palisades of Vogt. This limbal niche nourishes, protects, and regulates quiescence, self-renewal, and fate decision of limbal epithelial stem/progenitor cells (LEPCs) toward corneal epithelial differentiation. This review focuses on our current understanding of the mechanism by which limbal (stromal) niche cells (LNCs) regulate the aforementioned functions of LEPCs...

PURPOSE: To evaluate the clinical outcomes of self-retained cryopreserved amniotic membrane (cAM) for the treatment of corneal ulcers. METHODS: This was a single-center, retrospective review of consecutive patients with non-healing corneal ulcers that underwent treatment with self-retained cAM (PROKERA® Slim). The primary outcome measure was time to complete corneal epithelialization. Ocular discomfort, corneal staining, corneal signs, and visual acuity were assessed at 1 week, 1 month, 3 months, and 6 months...

Purpose: Fibrosis or scarring is a pathological outcome of wound healing and is characterized by terminally differentiated myofibroblasts. Heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) is a unique matrix component purified from amniotic membrane that exerts an anti-inflammatory effect. Herein, we investigate whether HC-HA/PTX3 can also exert an antiscarring effect. Methods: Human corneal fibroblasts and myofibroblasts were seeded on plastic, immobilized HA or HC-HA/PTX3 or on plastic with or without soluble HA and HC-HA/PTX3 in DMEM+10% FBS, with or without AMD3100 or SB431542 in DMEM+ITS with or without transforming growth factor-β1 (TGF-β1)...

Neurotrophic keratitis (NK), a degenerative disease caused by damage to the trigeminal nerve, abolishes both tearing and blinking reflexes, thus causing the most severe forms of dry eye disease (DED). Conversely, the increasing severity of DED also leads to progressive loss of corneal nerve density, potentially resulting in NK. Both diseases manifest the same spectrum of corneal pathologies including inflammation and corneal epithelial keratitis, which can progress into vision-threatening epithelial defect and stromal ulceration...

The birth tissue is predominantly comprised of amniotic membrane (AM) and umbilical cord (UC), which share the same cell origin as the fetus. These versatile biological tissues have been used to treat a wide range of conjunctival and corneal conditions since 1940. The therapeutic benefits of the birth tissue stem from its anti-inflammatory and anti-scarring properties that orchestrate regenerative healing. Although the birth tissue also contains many cytokines, growth factors, and proteins, the heavy chain 1-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) matrix has been identified to be a major active tissue component responsible for AM/UC's multifactorial therapeutic actions...

No abstract text is available yet for this article.

OBJECTIVE: Despite significant improvement in spinal cord function after in utero spina bifida (SB) repair compared with traditional postnatal repair, over half of the children who undergo this procedure do not benefit completely. This lack of benefit has been attributed to closure methods of the defect, with subsequent spinal cord tethering at the repair site. Hence, a regenerative patch or material with antiinflammatory and anti-scarring properties may alleviate comorbidities with improved outcomes...

On ocular surface, corneal epithelial stem cells (SC) reside in limbus between cornea and conjunctiva. Pax6, an evolutionally conserved transcription factor essential for eye development, is expressed in post-natal corneal and limbal epithelia progenitors (LEPC) but not in underlying stroma. Because Pax6 is transiently expressed in developing corneal stroma and a subset of limbal and corneal stromal progenitors, we examined the role of Pax6 in limbal niche cells (LNC) in maintaining the phenotype of neural crest (NC) progenitors to support LEPC...

OBJECTIVE: Microbial infection has been reported to cause blepharitis, conjunctivitis and keratitis. We evaluated the safety and efficacy of a foam formulation of 2% 4-terpineol (T4O) against common ocular microorganisms. MATERIAL AND METHODS: The antimicrobial effect of a 2% T4O formulation was evaluated by the United States Pharmacopeia 51 (USP <51>) antimicrobial effectiveness test for 14 and 28 days, as well as by a Time Kill Study (ASTM E2315) with a 60 s exposure time...

To expand multi-potent progenitors from human trabecular meshwork (TM), we have created a new optimized method on two-dimensional (2D) followed by three-dimensional (3D) Matrigel in modified embryonic stem cell medium supplemented with 5% fetal bovine serum (MESCM + 5% FBS). The expanded TM cells were small cuboidal cells expressing TM markers such as AQP1, MGP, CHI3L1, and AnkG, embryonic stem cell (ESC) markers such as Oct4, Sox2, Nanog, and ABCG2, and neural crest (NC) markers such as p75NTR, FOXD3, Sox9, Sox10, and MSX1...

PURPOSE: To report the outcome of self-retained amniotic membrane after debridement in recurrent dendritic keratitis. OBSERVATIONS: A 70-year-old female with a recurrent dendritic corneal ulcer received debridement followed by placement of self-retained amniotic membrane. Five days after treatment, the patient experienced a complete resolution of symptoms, marked reduction of inflammation, complete re-epithelialization of the cornea and improvement of visual acuity...

PURPOSE: To present a case of successful treatment of immune-related severe dry eye disease (DED) by self-retained cryopreserved amniotic membrane (CAM) in conjunction with conventional and systemic immunotherapy. OBSERVATIONS: A 48-year-old female with a 10-year history of rheumatoid arthritis under systemic immunomodulation developed non-resolved severe ocular dryness, pain, photophobia and blurred vision due to corneal epithelial keratopathy OD much worse than OS despite topical artificial tears, steroids, cyclosporine, autologous serum drops, punctal plugs and scleral lens for the last 3 years...

AIMS: To report the clinical characteristics and correlation between meibomian gland dysfunction (MGD) and keratitis in young patients with ocular demodicosis. METHODS: Observational case series of 60 patients younger than 35 years with ocular demodicosis, of which the diagnosis was based on microscopic counting of Demodex folliculorum and D. brevis of epilated lashes. Severity of keratitis and MGD was graded by photography and meibography, respectively, in a masked fashion...

PURPOSE: To evaluate the therapeutic benefit of self-retained cryopreserved amniotic membrane in conjunction with oral antiviral therapy in herpetic epithelial keratitis. METHODS: Retrospective review of 4 patients with primary (1 eye) and recurrent (3 eyes) unilateral herpetic epithelial keratitis treated with cryopreserved amniotic membrane through the placement of the PROKERA Slim (PKS) (Bio-Tissue, Inc) in conjunction with oral acyclovir. Their symptoms, conjunctival inflammation, corneal staining, and visual acuity were compared before and after treatment...

Descemet's membrane (DM) helps maintain phenotype and function of corneal endothelial cells under physiological conditions, while little is known about the function of DM in corneal endothelial wound healing process. In the current study, we performed in vivo rabbit corneal endothelial cell (CEC) injury via CEC scraping, in which DM remained intact after CECs removal, or via DM stripping, in which DM was removed together with CECs. We found rabbit corneas in the CEC scraping group healed with transparency restoration, while there was posterior fibrosis tissue formation in the corneas after DM stripping on day 14...