[The early clinical efficacy of allogeneic corneal lens inlays in correction of hyperopia].

OBJECTIVE: To evaluate the safety, effectiveness and predictability of allogeneic corneal lens inlays in correcting hyperopia. METHODS: In this case series study. Twenty-one hyperopic patients (37 eyes) received allogeneic corneal lens inlays. The range of preoperative spherical equivalent was 3.25 to 10.00 D, and the mean value was (6.84 ± 2.79)D. All the cases were followed up for 3 months. Uncorrected and best corrected visual acuity and refraction were compared before and after operation. Corneal topography and optical coherence tomography were performed. Ocular response analyzer was used to evaluate the shifts of corneal hysteresis. RESULTS: No intraoperative or postoperative complications were found. Uncorrected distance and near visual acuities (UCDVA and UCNVA) were improved obviously after surgery UCDVA was improved from (4.64 ± 0.25) to (4.89 ± 0.14) (F = 5.919, P < 0.001), and UCNVA was improved from J4.94 to J1.18 (F = 4.926, P < 0.01). The UCNVA in 31 eyes (83.8%) was J1 at 3 months after surgery. Mild overcorrection was the state early after operation, and the refractive power was stable at 1 month after surgery. The average residual spherical equivalent was (-0.63 ± 0.94)D, which was improved significantly from (6.84 ± 2.79)D before surgery. There was no obvious hyperopic regression. The corneal biomechanics did not change before and after surgery. CONCLUSIONS: Allogeneic corneal lens inlays can be used to correct hyperopic eyes with good safety, effectiveness and predictability. It provides a new choice for hyperopic patients.

Defining progressive stages in the commitment process leading to embryonic lens formation.

The commitment of regions of the embryo to form particular tissues or organs is a central concept in development, but the mechanisms controlling this process remain elusive. The well-studied model of lens induction is ideal for dissecting key phases of the commitment process. We find in Xenopus tropicalis, at the time of specification of the lens, i.e., when presumptive lens ectoderm (PLE) can be isolated, cultured, and will differentiate into a lens that the PLE is not yet irreversibly committed, or determined, to form a lens. When transplanted into the posterior of a host embryo lens development is prevented at this stage, while ~ 3 h later, using the same assay, determination is complete. Interestingly, we find that specified lens ectoderm, when cultured, acquires the ability to become determined without further tissue interactions. Furthermore, we show that specified PLE has a different gene expression pattern than determined PLE, and that determined PLE can maintain expression of essential regulatory genes (e.g., foxe3, mafB) in an ectopic environment, while specified PLE cannot. These observations set the stage for a detailed mechanistic study of the genes and signals controlling tissue commitment.

Central role for the lens in cave fish eye degeneration.

Astyanax mexicanus is a teleost with eyed surface-dwelling and eyeless cave-dwelling forms. Eye formation is initiated in cave fish embryos, but the eye subsequently arrests and degenerates. The surface fish lens stimulates growth and development after transplantation into the cave fish optic cup, restoring optic tissues lost during cave fish evolution. Conversely, eye growth and development are retarded following transplantation of a surface fish lens into a cave fish optic cup or lens extirpation. These results show that evolutionary changes in an inductive signal from the lens are involved in cave fish eye degeneration.

The lens controls cell survival in the retina: Evidence from the blind cavefish Astyanax.

The lens influences retinal growth and differentiation during vertebrate eye development but the mechanisms are not understood. The role of the lens in retinal growth and development was studied in the teleost Astyanax mexicanus, which has eyed surface-dwelling (surface fish) and blind cave-dwelling (cavefish) forms. A lens and laminated retina initially develop in cavefish embryos, but the lens dies by apoptosis. The cavefish retina is subsequently disorganized, apoptotic cells appear, the photoreceptor layer degenerates, and retinal growth is arrested. We show here by PCNA, BrdU, and TUNEL labeling that cell proliferation continues in the adult cavefish retina but the newly born cells are removed by apoptosis. Surface fish to cavefish lens transplantation, which restores retinal growth and rod cell differentiation, abolished apoptosis in the retina but not in the RPE. Surface fish lens deletion did not cause apoptosis in the surface fish retina or affect RPE differentiation. Neither lens transplantation in cavefish nor lens deletion in surface fish affected retinal cell proliferation. We conclude that the lens acts in concert with another optic component, possibly the RPE, to promote retinal cell survival. Accordingly, deficiency in both optic structures may lead to eye degeneration in cavefish.

Psf2 plays important roles in normal eye development in Xenopus laevis.

PURPOSE: Psf2 (partner of Sld5 2) represents a member of the GINS (go, ichi, ni, san) heterotetramer [1] and functions in DNA replication as a "sliding clamp." Previous in situ hybridization analyses revealed that Psf2 is expressed during embryonic development in a tissue-specific manner, including the optic cup (retina) and the lens [2]. This article provides an analysis of Psf2 function during eye development in Xenopus laevis. METHODS: A morpholino targeted to Psf2 mRNA was designed to knockdown Psf2 translation and was injected into specific embryonic cells during early cleavage stages in the frog, Xenopus laevis. Injected embryos were assayed for specific defects in morphology, cell proliferation, and apoptosis. Synthetic Psf2 RNA was also co-injected with the morpholino to rescue morpholino-mediated developmental defects. It is well known that reciprocal inductive interactions control the development of the optic cup and lens. Therefore, control- and morpholino-injected embryos were used for reciprocal transplantation experiments to distinguish the intrinsic role of Psf2 in the development of the optic cup (retina) versus the lens. RESULTS: Morpholino-mediated knockdown of Psf2 expression resulted in dosage-dependent phenotypes, which included microphthalmia, incomplete closure of the ventral retinal fissure, and retinal and lens dysgenesis. Defects were also observed in other embryonic tissues that normally express Psf2 including the pharyngeal arches and the otic vesicle, although other tissues that express Psf2 were not found to be grossly defective. Eye defects could be rescued by co-injection of synthetic Psf2 RNA. Examination of cell proliferation via an antibody against phospho-histone H3 S10P revealed no significant differences in the retina and lens following Psf2 knockdown. However, there was a significant increase in the level of apoptosis in retinal as well as forebrain tissues, as revealed by TUNEL (terminal deoxynucleotide transferase dUTP nick end labeling) assay. CONCLUSIONS: The results demonstrate intrinsic roles for Psf2 in both retinal and to a lesser extent, lens tissues. Observed lens defects can mainly be attributed to deficiencies in retinal development and consequently the late phase of lens induction, which involves instructive cues from the optic cup. Developmental defects were not observed in all tissues that express Psf2, which could be related to differences in the translation of Psf2 or redundant effects of related factors such as proliferating cell nuclear antigen (PCNA).

Light scattering levels from intraocular lenses extracted from donor eyes.

PURPOSE: To assess light scatter levels of intraocular lenses (IOLs) extracted from donor eyes to understand straylight elevation documented earlier in pseudophakic population studies and identify potential sources of light scattering in IOLs. SETTING: Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands. DESIGN: Experimental study. METHODS: Light scattering in 74 donor IOLs was measured with the C-Quant device adapted for in vitro analysis of IOLs. Straylight was assessed at a 2.5-degree and 7.0-degree scatter angle, and results were compared with the straylight of a 20-year-old crystalline lens, a 70-year-old crystalline lens, and a lens with cataract. To identify potential changes to the IOL material, the IOLs were examined with a light microscope and a slitlamp. RESULTS: At 2.5 degrees and 7.0 degrees, the straylight parameter was 5.78 deg2/steradian (sr) ± 4.70 (SD) and 5.06 ± 4.01 deg2/sr, respectively. Forty-one percent of IOLs showed lower straylight than the 20-year-old lens. In 14%, the scattering intensity was higher than in the 70-year-old lens; none showed straylight comparable to that of the cataractous lens. Increased straylight was associated with surface deposits, snowflake-like degeneration, and glistenings. The incidence of IOL-related complications differed between the IOL groups. CONCLUSIONS: Microscopic structural alterations of IOLs play a major role in straylight elevations in pseudophakic eyes. A clear correlation with degeneration and/or alteration of implanted IOLs was found. Although these IOL-related complications would likely not affect visual acuity, they give rise to straylight and thus can cause disability glare and other symptoms.

Zebrafish Hsp70 is required for embryonic lens formation.

Heat shock proteins (Hsps) were originally identified as proteins expressed after exposure of cells to environmental stress. Several Hsps were subsequently shown to play roles as molecular chaperones in normal intracellular protein folding and targeting events and to be expressed during discrete periods in the development of several embryonic tissues. However, only recently have studies begun to address the specific developmental consequences of inhibiting Hsp expression to determine whether these molecular chaperones are required for specific developmental events. We have previously shown that the heat-inducible zebrafish hsp70 gene is expressed during a distinct temporal window of embryonic lens formation at normal growth temperatures. In addition, a 1.5-kb fragment of the zebrafish hsp70 gene promoter is sufficient to direct expression of a gfp reporter gene to the lens, suggesting that the hsp70 gene is expressed as part of the normal lens development program. Here, we used microinjection of morpholino-modified antisense oligonucleotides (MOs) to reduce Hsp70 levels during zebrafish development and to show that Hsp70 is required for normal lens formation. Hsp70-MO-injected embryos exhibited a small-eye phenotype relative to wild-type and control-injected animals, with the phenotype discernable during the second day of development. Histological and immunological analysis revealed a small, underdeveloped lens. Numerous terminal deoxynucleotidyl transferase-mediated dUTP-fluoroscein nick-end labeling (TUNEL)-positive nuclei appeared in the lens of small-eye embryos after 48 hours postfertilization (hpf), whereas they were no longer apparent in untreated embryos by this age. Lenses transplanted from hsp70-MO-injected embryos into wild-type hosts failed to recover and retained the immature morphology characteristic of the small-eye phenotype, indicating that the lens phenotype is lens autonomous. Our data suggest that the lens defect in hsp70-MO-injected embryos is predominantly at the level of postmitotic lens fiber differentiation, a result supported by the appearance of mature lens organization in these embryos by 5 days postfertilization, once morpholino degradation or dilution has occurred.

A laboratory animal model for phacoemulsification practice.

A human cataract, removed in its capsule, and implanted in either the anterior or posterior aqueous chamber of a rabbit eye, provided a model system that simulated a clinical case of human senile cataract. Such a model can be used for practice surgery or for evaluation of an instrument designed to remove a cataract through a small incision.

Antibody response following implantation of xenogenic lenticules.

Rabbits underwent implantation of either lyophilized or fresh porcine lenticules into the central or peripheral cornea. All animals were followed for up to four months by slit-lamp examination and macrophotography to determine implant rejection. Serum antibody levels to soluble porcine cornea extract were determined by an enzyme-linked immunosorbant assay. Only those animals receiving lenticules into the peripheral cornea experienced a rejection and developed an antibody response to the porcine cornea extract. The production of antibody preceded the appearance of vascularization of the implanted lenticules. Thus, the site of lenticule implantation, not the type of tissue preparation, determined the outcome of the graft.

Adapting biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels for pigment epithelial cell encapsulation and lens regeneration.

This study investigated the encapsulation of newt iris pigment epithelial cells (PECs), which have the ability to regenerate a lens by trans-differentiation in vivo, within a biodegradable hydrogel of oligo(poly(ethylene glycol) fumarate) crosslinked with poly(ethylene glycol)-diacrylate. Hydrogel beads of initial diameter of 1 mm were fabricated by a molding technique. The swelling ratio and degradation rate of the hydrogel beads decreased with increasing crosslinking ratios. Confocal microscopy confirmed the cytocompatibility of crosslinking hydrogel formulations as evidenced by the viability of an encapsulated model cell line within a crosslinked hydrogel bead. Hydrogel beads encapsulating iris PECs were also implanted into lentectomized newts in vivo; histological evaluation of explants after 30 days revealed a regenerated lens, thus demonstrating that the presence of degrading hydrogel did not adversely affect lens regeneration. The results of this study suggest the potential of a method for lens regeneration involving oligo(poly(ethylene glycol) fumarate) hydrogels for iris PEC encapsulation and transplantation.