Glaucoma is a disease frequently associated with elevated intraocular pressure that can be alleviated by filtration surgery. However, the post-operative subconjunctival scarring response which blocks filtration efficiency is a major hurdle to the achievement of long-term surgical success. Current application of anti-proliferatives to modulate the scarring response is not ideal as these often give rise to sight-threatening complications. SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein involved in extracellular matrix (ECM) production and organization. In this study, we investigated post-operative surgical wound survival in an experimental glaucoma filtration model in SPARC-null mice. Loss of SPARC resulted in a marked (87.5%) surgical wound survival rate compared to 0% in wild-type (WT) counterparts. The larger SPARC-null wounds implied that aqueous filtration through the subconjunctival space was more efficient in comparison to WT wounds. The pronounced increase in both surgical survival and filtration efficiency was associated with a less collagenous ECM, smaller collagen fibril diameter, and a loosely-organized subconjunctival matrix in the SPARC-null wounds. In contrast, WT wounds exhibited a densely packed collagenous ECM with no evidence of filtration capacity. Immunolocalization assays confirmed the accumulation of ECM proteins in the WT but not in the SPARC-null wounds. The observations in vivo were corroborated by complementary data performed on WT and SPARC-null conjunctival fibroblasts in vitro. These findings indicate that depletion of SPARC bestows an inherent change in post-operative ECM remodeling to favor wound maintenance. The evidence presented in this report is strongly supportive for the targeting of SPARC to increase the success of glaucoma filtration surgery.
Current treatments for reversible blindness caused by corneal endothelial cell failure involve replacing the failed endothelium with donor tissue using a one donor-one recipient strategy. Due to the increasing pressure of a worldwide donor cornea shortage there has been considerable interest in developing alternative strategies to treat endothelial disorders using expanded cell replacement therapy. Protocols have been developed which allow successful expansion of endothelial cells in vitro but this approach requires a supporting material that would allow easy transfer of cells to the recipient. We describe the first use of plastic compressed collagen as a highly effective, novel carrier for human corneal endothelial cells. A human corneal endothelial cell line and primary human corneal endothelial cells retained their characteristic cobblestone morphology and expression of tight junction protein ZO-1 and pump protein Na+/K+ ATPase α1 after culture on collagen constructs for up to 14 days. Additionally, ultrastructural analysis suggested a well-integrated endothelial layer with tightly opposed cells and apical microvilli. Plastic compressed collagen is a superior biomaterial in terms of its speed and ease of production and its ability to be manipulated in a clinically relevant manner without breakage. This method provides expanded endothelial cells with a substrate that could be suitable for transplantation allowing one donor cornea to potentially treat multiple patients.
Our Slc4a11 KO mouse model successfully represents clinical manifestations of human CHED. We were able to show chronological corneal progression for the first time in a knockout mouse model as well as renal abnormalities.
PURPOSE.To characterize the clinical profile of femtosecond lenticule extraction (FLEx) correlated with ultrastructural analysis of the corneal interface and in vivo real-time intraocular pressure (IOP). METHODS. Prospective clinical case series with experimental studies; consecutive patients underwent FLEx at a single tertiary center over 10 months with postsurgical follow-up of 3 months. The patients were divided into three groups according to spherical equivalence (SE) (A, Ͻ Ϫ5.0 diopters [D]; B, Ն Ϫ5.00 D and Ͻ Ϫ9.00 D; and C, Ն Ϫ9.0 D). Twelve human cadaveric eyes analyzed using scanning electron microscopy after receiving FLEx; 40 rabbit eyes received FLEx with in vivo IOP measurements. The main outcome measures were refractive outcomes from study subjects; with corneal interface and IOP in experimental studies. RESULTS. Thirty-three subjects (22 females, 66.7%) underwent FLEx in both eyes (66 eyes). Mean age was 32 years (range, 21 to 46 years). Preoperative mean SE was Ϫ5.77 Ϯ 2.04 D with astigmatism of Ϫ1.03 Ϯ 0.72 D. There was a slight hyperopic shift (mean SE 0.14 Ϯ 0.53 D); 94% achieved uncorrected visual acuity Ն20/25 3 months postoperatively. Refractive stability was achieved within 1 month (P Ͻ 0.001). Ultrastructurally, the smoothness of the corneal interface was independent of ablation depth (mean irregularity scores A, B, C: 8.8 Ϯ 0.6, 10.3 Ϯ 0.4, 8.7 Ϯ 0.6, respectively; P ϭ 0.88). The increase in IOP during FLEx was similar to that in femtosecond (FS)-LASIK, albeit a twofold duration of raised IOP in FLEx (P Ͻ 0.001). CONCLUSIONS. These results suggest that FLEx is predictable and effective in treating myopia and myopic astigmatism. Experimental studies support the early clinical results and safety of this procedure. (Invest Ophthalmol Vis Sci. 2012;53: 1414 -1421) DOI:10.1167/iovs.11-8808 T he femtosecond (FS) laser is a near-infrared neodymiumdoped yttrium aluminum garnet (ND:YAG) laser that photodisrupts the cornea with surgical precision through plasma cleavage of stromal lamellae.1 The first commercial ophthalmic FS laser was introduced into the market in 2001 for laser in situ keratomileusis (LASIK) flaps. Since then, significant improvements in laser energy profiles, spatial resolution, and faster laser speeds have occurred.2 FS lasers have thus made a significant impact on refractive surgery by enabling nonmechanical creation of a corneal flap during LASIK. The FS laser offers several advantages over manual microkeratomes including increased precision, reduced incidence of flap complications, and the ability to cut thinner flaps without the risk of buttonhole formation.3,4 Moreover, newer generation FS lasers have reduced problems such as transient lightsensitivity syndrome and interference by cavitation bubbles. 5,6
To evaluate the difference in endothelial cell damage between 2 donor insertion techniques for Descemet stripping automated endothelial keratoplasty (DSAEK). Design: Experimental study and prospective case series. Thirty donor corneas and 10 patients undergoing DSAEK with glide insertion were included. Donor cornea lenticules were prepared and a wet lab DSAEK model established. Donor lenticules were inserted either by a "taco" fold (n= 15) or glide insertion (n = 15). Endothelial cell damage was assessed by scanning electron microscopy (n=20) and trypan blue exclusion (n=10). Endothelial cell count was assessed by specular microscopy in the clinical patients. Results: Endothelial cell viability and scanning electron microscopy demonstrated 2 different patterns of cell damage in either group. Cell viability and scanning electron microscopy showed there was mean cell damage of 9% and 9.2% , respectively, following glide insertion and 32% and 38%, respectively, following the taco-folded insertion (P =.004). The mean (SD) cell loss in the clinical patients following glide insertion was 25.3% (4.3%) at 6 months. Conclusion: Endothelial cell damage was higher in a wet lab model following taco-folded insertion compared with glide insertion. Initial clinical results with glide insertion showed satisfactory endothelial cell loss at 6 months. Clinical Relevance: Folding of the corneal tissue during DSAEK causes more endothelial damage than glide insertion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.