Stem cell grafting improves both motor and cognitive impairments in a genetic model of Parkinson's disease, the aphakia (ak) mouse.

Stem cell-based cell replacement of lost midbrain dopamine (mDA) neurons is a potential therapy for Parkinson's disease (PD). Toward this goal, it is critical to optimize various aspects of cell transplantation and to assess functional recovery through behavioral tests in validated animal model(s) of PD. At present, cell transplantation studies are being done almost exclusively in neurotoxin-based animal models, because few genetic models of PD exhibit robust mDA neuronal loss. Here we used a genetic model of PD, the aphakia mouse, which demonstrates selective degeneration of mDA neurons in the substantia nigra. We systematically investigated the functional effects of transplanting embryonic stem cell-derived cells at different stages of in vitro differentiation: embryoid body (EB), neural progenitor (NP), and neuronal differentiated (ND) stages. We found that transplantation of NP cells yielded the best outcomes for both survival and behavioral improvement, while transplantation of EB and ND cells resulted in high teratoma-like tumor formation and poor survival, respectively. In behavioral paradigms specific to basal ganglia, the NP cells group prominently improved motor behavioral defects 1 and 2 months posttransplantation. Furthermore, we found that NP cell transplantation also improved cognitive impairments of aphakia mice, as examined by the passive avoidance task. Importantly, these graft-induced functional improvements well correlated with survival of tyrosine hydroxylase-positive DA neurons. Taken together, we propose that the aphakia mouse can serve as a novel and useful platform for cell transplantation studies to assess both neurological and cognitive improvements and that NP stage cells represent an optimal stage for transplantation.

Bilateral microphthalmia and aphakia associated with multiple eye abnormalities in a free-living European red deer calf (Cervus elaphus).

A free-living European red deer calf (Cervus elaphus) was euthanized due to bilateral microphthalmia. Lens was missing, replaced by proliferating squamous epithelial cells; hyperplastic squamous cells, sebaceous and mucinous glands were observed within the cornea with the characteristics of inclusion cyst. Findings were consistent with congenital microphthalmia/aphakia, with multiple eye abnormalities.

Small-incision iris fixation of foldable intraocular lenses in the absence of capsule support.

PURPOSE: To report visual outcomes and complications of modified McCannel iris suture fixation of small-incision foldable acrylic intraocular lenses (IOLs) for aphakia in the absence of capsule support. DESIGN: Retrospective interventional case series. PARTICIPANTS: Forty-six patients who underwent foldable acrylic IOL implantation using peripheral iris suture fixation for aphakia in the absence of capsule support. METHODS: Data from 46 patients who underwent iris fixation of a foldable acrylic IOL were retrospectively evaluated for underlying diagnoses, surgical history, clinical results, and complications. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity (BCVA), spherical equivalent, and surgical complications. RESULTS: Best-corrected visual acuity improved from 20/100 to 20/50 (P = 0.01), with 97% of eyes maintaining or improving BCVA after a mean (+/- standard deviation) follow-up of 24.1+/-12.4 months. Complications included transient low-grade uveitis (3 [6.5%]), transient pigment dispersion (3 [6.5%]), IOL dislocation (2 [4.3%]), elevated intraocular pressure (1 [2.2%]), and retinal detachment (1 [2.2%]). No new cases of cystoid macular edema or worsening of glaucoma occurred. CONCLUSION: Small-incision peripheral iris fixation of 3-piece acrylic foldable IOLs in the absence of capsule support appears to be an effective technique with few severe adverse events.

Congenital corneal staphyloma associated with aphakia.

A neonate had a globular mass bulging through the eyelids of the left eye. Computed tomography revealed a large ectatic corneal lesion and the absence of a lens. The enucleated globe revealed that the posterior surface of the ectatic cornea was lined by iris tissue, indicating corneal staphyloma.

Optical and ultrasound measurement of axial length and anterior chamber depth for intraocular lens power calculation.

PURPOSE: To evaluate the precision, reproducibility, and applicability of an optical method based on partial coherence interferometry for intraocular lens (IOL) power calculation. SETTING: Ultrasound laboratory of a university eye hospital. METHODS: A prospective comparison of measurements made by the IOLMaster optical instrument (Carl Zeiss) and Ultrascan Digital 2000 contact ultrasound A-scan (Alcon) for IOL calculations was performed. Examined were 255 eyes of 134 persons (204 phakic, 47 pseudophakic, and 4 aphakic). The mean age of the patients was 67.9 years (range 7 to 94 years). RESULTS: The IOLMaster measurements were successful in more than 80% of cases: in 82%, 99%, and 99% for axial length (AL), anterior chamber depth (ACD), and keratometry measurements, respectively. The reproducibility of the AL and ACD measurements was very high (coefficient of variation 0.13% and 2.20%, respectively). The AL and ACD values were significantly larger with the IOLMaster (P <.001) than with the Ultrascan Digital 2000. The correlation between ultrasound and optical AL measurements was high (r = 0.985; P <.001); however, there was no correlation between ACD measurements (r = 0.079; P =.397). The corneal refractive power measurements of a Javal-type keratometer and the IOLMaster were highly correlated (r = 0.955; P <.001), with a mean difference of 0.2 diopter. CONCLUSIONS: The results show that measurements for IOL calculation are easy and precise with the optical method. It is a noncontact method, so no anesthesia is needed and there is no risk of infection.

Congenital aphakia: a clinicopathologic report of three cases.

BACKGROUND: Congenital aphakia is a rare condition that has been classified as primary when no lens induction of the surface ectoderm occurs and secondary when lens development takes place but later is resorbed or expelled in utero. METHODS: The authors report the clinical and pathologic findings in three infants with congenital aphakia whose eyes were enucleated either at surgery at 11 months or at autopsy after 1 and 3 days of life. RESULTS: Two cases classified as primary congenital aphakia had severe microphthalmos, anterior segment aplasia, or anomalous development and posterior choroidal and optic disc colobomas. One was in a case believed to be Waardenburg's recessive anophthalmia syndrome and the other had 18 trisomy. A case of secondary congenital aphakia had findings of Peter's syndrome and features suggesting rubella, which had been observed in some previous reports. CONCLUSIONS: Primary congenital aphakia can result from a variety of teratogenic events in the first 4 weeks of embryogenesis and results in microphthalmos and severe anterior segment aplasia/dysplasia. Secondary congenital aphakia is associated with less severe ocular anomalies. The possible role of deletion or mutation involving the PAX6 gene in anterior segment anomalies and induction of lens development is discussed. In addition to chromosomal influences, in utero viral infection, particularly rubella, may play a role in some cases.

The HNK-1 epitope in the pseudophakic and aphakic eye and secondary cataract.

PURPOSE: To search for changes in the presence and distribution of the cell-adhesion-related HNK-1 carbohydrate epitope after cataract extraction. METHODS: Twenty-five pseudophakic and two aphakic human autopsy eyes and, for comparison, one anterior subcapsular cataract obtained at surgery were studied with monoclonal antibodies (MAbs) HNK-1 and NC-1 to the HNK-1 epitope using the avidin-biotinylated peroxidase complex method. RESULTS: MAbs to the HNK-1 epitope constantly immunolabelled the inner connective tissue layer of the ciliary body in all pseudophakic and aphakic eyes studied. The distribution of the immunoreaction was similar to that reported for normal eyes. They also labelled the extracellular matrix in each of 18 plaques of secondary cataract on the posterior capsule, in each of 13 plaques at the rim of the capsular bag, and in the anterior subcapsular cataract. Bladder cells in each of 16 Soemmering's rings remained unlabelled. CONCLUSION: The distribution of the HNK-1 epitope in the ciliary body does not appreciably change after cataract extraction, although the accommodative demand of the eye is altered. Its presence in an anterior subcapsular cataract suggests that the epitope may be locally produced by lens epithelial cells also in secondary cataract. The epitope is associated with cell adhesion and migration, both of which may play a role in the pathogenesis of secondary cataract.

Congenital aphakia in Peters' anomaly syndrome. A case report.

The authors report a case of congenital bilateral corneal opacities in which one of the eyes was enucleated because of malignant glaucoma and corneal perforation. Corneal defects and iridocorneal adhesion were found, but aphakia was the major pathologic ocular finding. The clinical picture and pathology study indicated this case as a Peters' anomaly presenting congenital aphakia.

Relationship of cell death to cyclophosphamide-induced ocular malformations.

C57BL/6J mice were used to study the ocular teratogenic effects of cyclophosphamide administered to pregnant females on d 9 of pregnancy at a dose of 5 mg/kg body weight. Nile blue staining demonstrated increased cell death at the base of the optic stalk, in the optic vesicle, and in the perivesicular mesenchyme in treated embryos. Malformations studied at gestational d 11 and 16 by light and scanning electron microscopy included microphthalmos, microphakia, and aphakia and were predictable based upon patterns of increased cell death. These anomalies are similar to those reported with exposure to ethanol or isotretinoin on gestational d 7.

A prospective study on the implantation of anterior chamber intraocular lenses during keratoplasty for pseudophakic and aphakic bullous keratopathy.

Between April 1986 and April 1989, the authors conducted a prospective study of the use of open-loop anterior chamber intraocular lenses (AC IOLs) in patients undergoing penetrating keratoplasty for pseudophakic bullous keratopathy or monocular aphakic bullous keratopathy. All patients underwent the same operation--a penetrating keratoplasty combined with insertion of an open-loop AC IOL. Pseudophakic patients had an IOL exchange at the time of surgery. Thirty-six patients have been followed an average of 15 months. Thirty-two (89%) of the grafts are clear. Preoperatively, 100% of eyes had visual acuity less than 20/200. Postoperatively, 11 eyes (31%) have visual acuity better than 20/40 and 23 eyes (64%) have visual acuity better than 20/100. The most common causes for visual acuity less than 20/200 were cystoid macular edema, glaucoma, and immunologic graft failure. Using open-loop AC IOLs in patients with pseudophakic or aphakic bullous keratopathy can give good postoperative results and functional vision.

The nationwide study of epikeratophakia for aphakia in older children.

A nationwide study of epikeratophakia for aphakia in older children was conducted from March 1984 to March 1986. Sixty-three patients, 8 to 18 years of age, underwent this procedure in 65 eyes. Twenty-eight patients had congenital cataracts and 35 had traumatic cataracts. Fifty-one of the 65 eyes were aphakic at the time of surgery (secondary procedures). All surgeries were successful; no tissue lenses were lost or removed. Postoperatively, 73% of the patients were within 3 diopters (D) of emmetropia. The patients with congenital cataracts gained an average of one Snellen line of best-corrected visual acuity; patients with traumatic cataracts lost an average of one Snellen line of best-corrected visual acuity. In older pediatric patients, epikeratophakia appears to be a safe and effective procedure for the correction of aphakia.

ATPase pump site density in human dysfunctional corneal endothelium.

Proper corneal hydration is maintained by a Na, K-ATPase pump located in the lateral membranes of the endothelial cells. In dysfunctional corneas this pumping action appears to break down as the corneas become edematous. In order to provide quantitative and qualitative data on the Na, K-ATPase pump site density on dysfunctional and functional human corneal endothelial cells, the present study has employed both autoradiographic and histochemical techniques. Computer-assisted morphometrics and statistical analysis showed that there was a significant reduction (P less than 0.001) in 3H-ouabain binding, and thus ATPase pump sites, in the three types of corneas (Fuchs' endothelial dystrophy, aphakic and pseudophakic bullous keratopathy) with dysfunctional endothelia as compared to both types of corneas (eye bank, keratoconus) with functional endothelial cells. There were no significant differences amongst the dysfunctional types or between the two functional types of corneal endothelial cells in respect to density of silver grains. Histochemical staining for ATPase showed less p-nitro-phenylphosphatase histochemical reaction product present on dysfunctional endothelial lateral membranes than in the functional cells.

The nationwide study of epikeratophakia for aphakia in children.

In the nationwide study of epikeratophakia, 97 surgeons performed a total of 335 procedures in 314 eyes for the correction of aphakia in children under the age of 8 years 1 month. Fifteen children underwent bilateral surgery. Thirty-six tissue lenses were removed and 21 of these eyes underwent a second epikeratophakia procedure. Overall, the success rate for procedures was 89%, and with repeated surgery it was 95% for eyes. Seventy-three percent of the patients were within 3 diopters of emmetropia after surgery. Visual acuity results in patients able to provide verbal responses to the illiterate E, Allen card, or Snellen line chart testing showed improvement in most cases. The safety of epikeratophakia makes it a desirable option for the correction of aphakia in children who are spectacle or contact-lens intolerant, and the permanence of the correction eliminates the problem of optical noncompliance.

Posterior uveal melanomas in aphakic and pseudophakic eyes.

Of 650 eyes with posterior uveal melanomas that were accessioned at the Armed Forces Institute of Pathology from 1975 to 1983, 28 were aphakic and eight were pseudophakic. In ten of these 36 cases, the cataract had been unilateral. Only two patients had been examined with preoperative A-scan ultrasonography to obtain the axial length of the eye. None of the patients had been examined for possible intraocular tumors by either A- or B-scan ultrasonography. We believe that in many of these cases the tumor was large enough to have been detected at the time of cataract surgery. Thus, if the lens is too opaque for the fundus to be viewed, B-scan ultrasonography should be used before cataract extraction.

Intracorneal lens implantation.

In previous experiments, we found that a high-water-content hydroxyethyl methacrylate (Permalens) hydrogel implant was not only well tolerated within the rabbit corneal stroma but also would successfully alter the anterior radius of curvature, and thus the refractive state, of the rabbit eye. The same lens material implanted in the cornea of a patient with aphakic bullous keratopathy was tolerated for six months and decreased epithelial edema but did not alter the refractive state. This cornea, containing the intrastromal lens, was obtained at subsequent penetrating keratoplasty and studied by light and transmission electron microscopy. Morphologically, the epithelium and anterior stroma were not edematous, whereas the stroma posterior to the lens remained edematous. Minimal fibroblastic activity was evident at the lens-stroma interface. There were no signs of inflammation, ulceration, or neovascularization.