Injectable, Antioxidative, and Tissue-Adhesive Nanocomposite Hydrogel as a Potential Treatment for Inner Retina Injuries.

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non-arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS-related challenges, this study focuses on creating an injectable and tissue-adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin-modified hydrogel with photo-crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin-loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

In vivo confocal microscopic findings of corneal wound healing after corneal epithelial debridement in diabetic vitrectomy.

PURPOSE: To study healing of corneal wounds using in vivo confocal microscopy in patients who received corneal epithelial debridement during pars plana vitrectomy for proliferative diabetic retinopathy and to investigate risk factors for delayed healing. DESIGN: Prospective, observational case series. PARTICIPANTS: Forty-four eyes of 40 patients were enrolled. METHODS: In vivo confocal microscopy was used to evaluate selected images of the corneal basal and apical surface epithelial cells and subbasal nerves before surgery, weekly for the first month, and at 3 and 6 months after surgery. Slit-lamp biomicroscopy was carried out at the same time. Multiple linear regression analysis of selected potential risk factors was performed to investigate the main determinants of delayed corneal healing. MAIN OUTCOME MEASURES: Healing rate of corneal epithelial cells and subbasal nerves and factors influencing the healing. RESULTS: By slit-lamp biomicroscopy, corneal epithelial defects were found in 22.8% of eyes at 2 weeks and in 5.4% at 1 month after surgery. In vivo confocal microscopy demonstrated incomplete healing of basal epithelial cells in 72.1%, 15.2%, and 0% of eyes and incomplete healing of surface apical epithelial cells in 81.1%, 9.1%, and 0% of eyes at 1, 3, and 6 months after surgery. The percentage of subbasal nerves regaining preoperative appearance was 0%, 6.8%, and 89.3% at 1, 3, and 6 months after surgery. Regression analysis revealed infusion of silicone oil (P = 0.020) and C(3)F(8) (P = 0.017) resulted in delayed healing by slit-lamp biomicroscopy; age (P = 0.028), diabetic treatment regimen (P = 0.014), and scleral buckling (P = 0.001) correlated with delayed recovery of basal cells by in vivo confocal microscopy. The latter 2 factors also were related to delayed reconformation of apical cells (P = 0.011 and 0.004, respectively). Neither healing of apical and basal cells showed a significant correlation to findings by slit-lamp biomicroscopy (r = 0.19 and 0.09). CONCLUSIONS: Healing of corneal epithelial wounds in diabetic eyes is slow. Both the basal and apical epithelial layers were involved in the slow healing process. Age, diabetic treatment regimen, and several intraoperative factors may alter healing rates. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Improvements in vision-related quality of life with AcrySof IQ SN60WF aspherical intraocular lenses.

PURPOSE: To compare vision-related quality of life and higher-order aberrations (HOAs) with an aspherical intraocular lens (IOL) (AcrySof IQ SN60WF) and a conventional spherical IOL (AcrySof SA60AT) (both Alcon) after phacoemulsification. SETTING: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China. METHODS: Sixty-five patients were prospectively randomized to receive an Alcon AcrySof IQ SN60WF IOL (30 eyes) or an AcrySof SA60AT IOL (35 eyes). All patients had a complete ophthalmologic examination including uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), and wavefront analysis preoperatively and 3 months postoperatively. Patients also completed the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) to evaluate vision-related quality of life. RESULTS: The mean postoperative BSCVA (logMAR) was 0.09 +/- 0.07 (SD) in the aspherical IOL group and 0.12 +/- 0.08 in the spherical IOL group; the difference was not statistically significant. Spherical aberrations were statistically significantly lower in the aspherical IOL group (mean 0.12 +/- 0.23 microm) than in the spherical IOL group (mean 0.33 +/- 0.20 microm) (P = .001). Both IOL types improved most aspects of patients' vision-related quality of life. The aspherical IOL group had clinically significant improvement on more NEI VFQ-25 subscales, although the difference between groups in vision-related quality of life was not statistically significant. CONCLUSION: Eyes with the aspherical AcrySof IQ SN60WF IOL had reduced HOAs and spherical aberrations compared with eyes with the spherical AcrySof SA60AT IOL; however, there were no statistically significant differences in visual acuity or vision-related quality of life between groups.

Comparison of the bacteriostatic effects, corneal cytotoxicity, and the ability to seal corneal incisions among three different tissue adhesives.

PURPOSE: To compare the bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions among fibrin glue and 2 commercially available cyanoacrylate derivatives: N-butyl cyanoacrylate and methoxypropyl cyanoacrylate. METHODS: The bacteriostatic activities of these tissue glues were verified by measuring the zones of bacterial growth inhibition surrounding the adhesive droplets on agar plates inoculated with Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Mycobacterium chelonae. Corneal cytotoxicity was tested by a direct contact method by using cultured bovine corneal epithelial cells, keratocytes, and corneal endothelial cells challenged with droplets of adhesives. Each of the cells was treated with droplets of adhesives. The ability to seal corneal incisions was verified by calculating the maximum intraocular pressure resistant to leakage of rabbit corneal stab wounds sealed with tissue adhesives. RESULTS: Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate showed bacteriostatic effects against S. aureus, S. pneumoniae, and M. chelonae but not P. aeruginosa and E. coli. In contrast, fibrin glue had no such effects against either Gram-positive or -negative bacteria (P < 0.01). Methoxypropyl cyanoacrylate showed the highest levels of corneal cytotoxicity, followed by N-butyl cyanoacrylate. Fibrin glue, however, showed minimal cytotoxicity (P < 0.01). Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate also displayed a greater ability to seal corneal incisions than that of fibrin glue (P < 0.01). CONCLUSIONS: The bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions differed among the 3 compounds tested. These different properties should be considered when choosing tissue adhesives during corneal surgery.

Applications of Biomaterials in Corneal Endothelial Tissue Engineering.

When corneal endothelial cells (CECs) are diseased or injured, corneal endothelium can be surgically removed and tissue from a deceased donor can replace the original endothelium. Recent major innovations in corneal endothelial transplantation include replacement of diseased corneal endothelium with a thin lamellar posterior donor comprising a tissue-engineered endothelium carried or cultured on a thin substratum with an organized monolayer of cells. Repairing CECs is challenging because they have restricted proliferative ability in vivo. CECs can be cultivated in vitro and seeded successfully onto natural tissue materials or synthetic polymeric materials as grafts for transplantation. The optimal biomaterials for substrata of CEC growth are being investigated. Establishing a CEC culture system by tissue engineering might require multiple biomaterials to create a new scaffold that overcomes the disadvantages of single biomaterials. Chitosan and polycaprolactone are biodegradable biomaterials approved by the Food and Drug Administration that have superior biological, degradable, and mechanical properties for culturing substratum. We successfully hybridized chitosan and polycaprolactone into blended membranes, and demonstrated that CECs proliferated, developed normal morphology, and maintained their physiological phenotypes. The interaction between cells and biomaterials is important in tissue engineering of CECs. We are still optimizing culture methods for the maintenance and differentiation of CECs on biomaterials.

Fabrication of a bioengineered corneal endothelial cell sheet using chitosan/polycaprolactone blend membranes.

Our previous study has demonstrated cultivation of bovine corneal endothelial cells (BCECs) on the chitosan-polycaprolactone (PCL) blends. BCECs could grow well and express physiological phenotypes after PCL was introduced into chitosan by means of blending. The feasibility of using chitosan-PCL-blended membranes as scaffold and carrier for corneal endothelial cell (CEC) transplantation is worthy of more investigation. In this work, we attempt to manufacture various blended membranes to bring BCEC cultivation into harmony by hybridizing two polymers with fine adjustment. Therefore, chitosan, which does not promote BCECs maturation, and PCL, which supports, BCEC proliferation, are combined to prepare the blends. Analyses of transmittance, proliferative, abilities, phenotypic expressions, extracellular matrix (ECM) protein production, and hemotoxylin and eosin (H&E) staining were executed step-by-step. From our observations, the blended membranes united respective characteristics. The cultured BCECs on the blends illustrated normal appearance and good proliferative abilities. Immunohistochemical staining verified physiologically phenotypic expressions of ZO-1 and Na-K ATPase. Western blot analysis also confirmed the existence of collagen type IV proteins. Furthermore, the formation of a continuous monolayer of cells attached on the blended membrane was confirmed by H&E staining. These results suggested that chitosan-PCL blended membranes may be an optimized biomaterial to fabricate bioengineered corneal endothelium and show potential to facilitate CEC transplantation in the future.

The role of type III secretion system and lens material on adhesion of Pseudomonas aeruginosa to contact lenses.

PURPOSE: To determine the distribution of invasive and cytotoxic genotypes among ocular isolates of P. aeruginosa and investigate the influence of the type III secretion system (T3SS) on adhesion to conventional, cosmetic, and silicone hydrogel contact lenses (CL). METHODS: Clinical isolates from 2001 to 2010 were analyzed by multiplex PCR for exoS, exoU, and exoT genes. Bacterial adhesion to etafilcon, nelfilcon (gray colored), balafilcon, and galyfilcon CL with or without artificial tear fluid (ATF) incubation were compared. Surface characteristics were determined with scanning electron microscopy (SEM). RESULTS: Among 87 total isolates, 64 strains were from microbial keratitis cases. CL-related microbial keratitis (CLMK) isolates were mostly of the cytotoxic genotype (expressing exoU) (P = 0.002). No significant differences were found in bacterial adhesion to all types of CL between the genotypes under T3SS-inducing conditions. A trend for least bacterial adhesion of galyfilcon compared to the other CL was noted for both genotypes. Needle complex pscC mutants adhered less to all materials than the wild type (P < 0.05), indicating a role of the T3SS in contact lens adhesion. ATF-incubated CL had significantly more bacterial adhesion (P < 0.05). SEM showed most of the bacteria adhering on CL surfaces. CONCLUSIONS: CLMK isolates were mostly of cytotoxic genotype. Different genotypes did not significantly differ in its adhesion to various CL. T3SS and other adhesins are involved in bacteria-contact lens adhesion through complex interactions. Contact lens materials may also play an important role in the adherence of both genotypes of P. aeruginosa.