Opposite Eye Research Articles

Subfoveal choroidal thickness in multiple evanescent white dot syndrome

Background: Multiple evanescent white dot syndrome (MEWDS) is an inflammation of the choriocapillaris, which typically presents with unilateral vision loss and is characterised by the presence of multiple yellow‐white spots in the posterior pole to the midperipheral fundus. This study was conduced to evaluate subfoveal choroidal thickness between the acute and convalescent phases in two patients with MEWDS.Methods: Two young female Japanese patients underwent a comprehensive ophthalmic examination, including slitlamp biomicroscopy, funduscopy and both fluorescein and indocyanine green angiographies. The subfoveal choroidal and central retinal thicknesses were measured using Cirrus high‐definition spectral‐domain optical coherence tomography.Results: The two patients were diagnosed with unilateral MEWDS based on characteristic funduscopic and angiographic findings. The disrupted foveal inner segment–outer segment boundary line in the acute phase was restored in the convalescent phase in both patients. In the affected eye of Patient 1, the subfoveal choroidal thickness (337 µm) noted in the acute phase decreased to 249 µm at 133-days after the initial visit (convalescent phase). Similarly, the acute phase thickness (440 µm) in Patient 2 decreased to 358 µm at 133-days after the initial visit. The thickness in the asymptomatic opposite eye also decreased during the convalescent phase in both patients. In the acute phase, thickness in the affected eyes was greater than that in the opposite eyes in both patients. In contrast, central retinal thickness remained unchanged in both eyes during follow up in both patients.Conclusion: This is the first report to describe the relationship between subfoveal choroidal thickness and MEWDS. We found that the choroid was thicker in the acute phase than the convalescent phase in both the affected and opposite eyes of both patients, suggesting that an inflammatory reaction might occur in the choroidal stroma in addition to the choriocapillaris and might be bilateral rather than unilateral.

Characteristics of the filled-in surface at the blind spot

Our visual system can restore information missing within the portion of the retinal image corresponding to the blind spot where the optic nerve exits the eye. Previous studies of the properties of filled-in surfaces at the blind spot have found similarities and dissimilarities between filled-in and real surfaces and have therefore not provided a consistent view of the characteristics of the filled-in surface. First, we investigated whether filling-in utilizes a contour integration mechanism. Gratings with collinear lines filled in the blind spot more effectively than those both with orthogonal lines and without any line, suggesting that collinear facilitation underlies the filling-in of the blind spot. Second, the dynamics of binocular rivalry was examined by comparing the dominance duration distributions of filled-in and real surfaces. The results indicated that the strength of the filled-in surface was attenuated compared to that of the real surface during rivalry. Lastly, we tested whether travelling waves of dominance in rivalry could occur at the blind spot. The travelling waves could propagate through a hole only at the blind spot, suggesting that the filled-in surface helps perceptual waves to travel across the blind spot. These results suggest that the filled-in surface shares a common mechanism via a horizontal connection but that it has weak strength to suppress the opposite eye during binocular viewing.

Effects of antioxidant supplementation on mRNA expression of glucose-6-phosphate dehydrogenase, β-actin and 18S rRNA in the anterior capsule of the lens in cataract patients

This was a preliminary study of the effects of antioxidant supplementation on the peroxidation status of the lens by investigating mRNA expression of anti-oxidative enzymes in the lens. The mRNA expression levels of glucose-6-phosphate dehydrogenase (G6PDH), β-actin (β-ACT) and 18S rRNA (18S) were measured in this study because they are common reference genes for measuring mRNA levels by means of a real-time reverse transcription polymerase chain reaction (RT-PCR) in various tissues. Thirteen patients with binocular cataracts of the same grade were included in the study after giving informed consent. A piece of the anterior capsule, along with a sample of lenticular epithelial cells (LECs), was collected as a pre-intake sample during cataract surgery. Ocuvite + Lutein®, an antioxidant supplement, was administered orally beginning the day after surgery. Six weeks later, a piece of the anterior capsule along with a sample of LECs, was collected as a post-intake sample during cataract surgery of the opposite eye. RNA was purified from the homogenized samples, and cDNA was reverse transcribed to measure mRNA levels. The expression levels of G6PDH, 18S and β-ACT were measured using RT-PCR. The expression levels of G6PDH and 18S were significantly higher in the post-intake samples than they were in the pre-intake samples. Significant positive correlations between the expression levels of G6PDH and 18S were observed in both the pre- and post-intake samples. Following gender-specific analyses, the expression levels of G6PDH and 18S in the post-intake samples were found to be significantly higher among the female patients. A significant positive correlation between the expression levels of G6PDH and 18S was observed in the post-intake samples from the male patients. There were no significant changes in the gene expression levels of β-ACT after supplementation among male or female patients. β-ACT has been verified for use as a reference gene for measuring the effects of antioxidant supplementation in the lens by RT-PCR. Antioxidant supplementation was noted to increase G6PDH in the pentose phosphate cycle and 18S rRNA in the ribosome.

Influence of CD8+ T regulatory cells on intraocular tumor development

The interior of the eye, or uvea, is a site of immune privilege where certain immune responses are attenuated or completely excluded to protect non-regenerating tissues essential for vision. One consequence of this immunoregulation is compromised immune mediated elimination of intraocular tumors. For example, certain murine tumor cell lines which are rejected by host immune responses when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. Progressive ocular tumor growth occurs despite induction of tumor-specific CD8+ T cell responses capable of eliminating a subsequent tumor challenge in the skin or opposite eye. Why these CD8+ T effectors fail to eliminate established ocular tumors is not known. It is well appreciated that growth of tumors in the a.c. induces the generation of immunosuppressive CD8+ T regulatory (Treg) cells. However, the contribution of CD8+ Treg in ocular tumor progression remains unclear. Several studies indicate that these CD8+ Treg target responding CD4+ T cells to inhibit their induction of macrophage-dependent delayed type hypersensitivity (DTH) responses to tumor antigens (Ags). However, induction of tumor-specific CD4+ T cell responses does not assure intraocular tumor elimination. This review is focused on how CD8+ Treg could influence the tumoricidal activity of ocular tumor-specific CD8+ T effector cells.

Short-term Cell Death and Inflammation After Intracorneal Inlay Implantation in Rabbits

To investigate the cell death and inflammatory response to insertion of the KAMRA inlay (AcuFocus Inc) for presbyopia. Twenty-four rabbits were included in the study. Each rabbit had pockets generated in both corneas with a femtosecond laser. One eye of each rabbit had an inlay inserted into the pocket and the opposite control eye had the pocket dissected. Eight rabbits were studied at 24 hours, 48 hours, or 6 weeks after surgery. Tissue sections were analyzed with TUNEL assay to detect cell death and immunohistochemistry for CD11b to detect monocytes as a marker of inflammation. The inlay group had significantly more stromal cell death than the control group at 48 hours after surgery (P=.038). At 24 hours and 6 weeks after surgery, no significant difference was noted in stromal cell death between the inlay and control groups. Significantly more CD11b+ cells were noted in the stroma in the inlay group compared to the control group at 24 and 48 hours after surgery (P=.025 and P=.001, respectively). However, at 6 weeks after surgery, no significant difference in CD11b+ cells was observed between the control and inlay groups (P=.05). Although an early increase in stromal cell death and inflammation occurred in eyes that underwent femtosecond laser pocket creation and KAMRA inlay insertion compared to a control group with the pocket only, no significant difference was noted between the inlay and control groups in stromal cell death or inflammation at 6 weeks after surgery.

Isolation and Genetic Characterization of Mother-of-Snow-White, a Maternal Effect Allele Affecting Laterality and Lateralized Behaviors in Zebrafish

In the present work we report evidence compatible with a maternal effect allele affecting left-right development and functional lateralization in vertebrates. Our study demonstrates that the increased frequency of reversed brain asymmetries in a zebrafish line isolated through a behavioral assay is due to selection of mother-of-snow-white (msw), a maternal effect allele involved in early stages of left-right development in zebrafish. msw homozygous females could be identified by screening of their progeny for the position of the parapineal organ because in about 50% of their offspring we found an altered, either bilateral or right-sided, expression of lefty1 and spaw. Deeper investigations at earlier stages of development revealed that msw is involved in the specification and differentiation of precursors of the Kupffer's vesicle, a structure homologous to the mammalian node. To test the hypothesis that msw, by controlling Kupffer's vesicle morphogenesis, controls lateralized behaviors related to diencephalic asymmetries, we analyzed left- and right-parapineal offspring in a “viewing test”. As a result, left- and right-parapineal individuals showed opposite and complementary eye preference when scrutinizing a model predator, and a different degree of lateralization when scrutinizing a virtual companion. As maternal effect genes are expected to evolve more rapidly when compared to zygotic ones, our results highlight the driving force of maternal effect alleles in the evolution of vertebrates behaviors.

Leukocoria and Vitreous Hemorrhage as the Initial Manifestation of Sickle Retinopathy in a 3-Year, 6-Month-Old Child With Sickle Trait (AS)

The authors present the youngest reported child with proliferative sickle retinopathy. A 3-year, 6-month-old boy presented with leukocoria in the left eye, left esotropia, and dense free-floating white vitreous cells obscuring the fundus, suspicious for endophytic retinoblastoma. Ultrasonography depicted dense debris in the vitreous with no distinct calcific echo or retinal mass. Transcorneal, transzonular fine-needle aspiration biopsy of the vitreous confirmed the presence of dehemoglobinized vitreous red blood cells without tumor. The opposite eye showed peripheral retinal pigment epithelial proliferation and fibrosis with angiographic peripheral ischemia. Hemoglobin electrophoresis disclosed sickle trait (AS). The findings were classified as proliferative sickle cell retinopathy with vitreous hemorrhage in the left eye and non-proliferative sickle cell retinopathy in the right eye. Leukocoria generally raises warnings for retinoblastoma, but can also reflect chronic vitreous hemorrhage.

Direction discrimination thresholds in binocular, monocular, and dichoptic viewing: Motion opponency and contrast gain control

We studied the binocular organization of motion opponency and its relationship to contrast gain control. Luminance contrast thresholds for discriminating direction of motion were measured for drifting Gabor patterns (target) presented on counterphase flickering Gabor patterns (pedestal). There were four presentation conditions: binocular, monocular, dichoptic, and half-binocular. For the half-binocular presentation, the target was presented to one eye while pedestals were presented to both eyes. In addition, to test for motion opponency, we studied two increment and decrement conditions, in which the target increased contrast for one direction of movement but decreased it for the opposite moving component of the pedestal. Threshold versus pedestal contrast functions showed a dipper shape, and there was a strong interaction between pedestal contrast and test condition. Binocular thresholds were lower than monocular thresholds but only at low pedestal contrasts. Monocular and half-binocular thresholds were similar at low pedestal contrasts, but half-binocular thresholds became higher and closer to dichoptic thresholds as pedestal contrast increased. Adding the decremental target reduced thresholds by a factor of two or more-a strong sign of opponency-when the decrement was in the same eye as the increment or the opposite eye. We compared several computational models fitted to the data. Converging evidence from the present and previous studies (Gorea, Conway, & Blake, 2001) suggests that motion opponency is most likely to be monocular, occurring before direction-specific binocular summation and before divisive, binocular gain control.

Direction discrimination thresholds in binocular, monocular, and dichoptic viewing: Motion opponency and contrast gain control

Purpose: The present study investigated the binocular organization of motion opponency and its relation to contrast gain control. Method: We measured luminance contrast thresholds for discriminating direction of motion for drifting Gabor patterns (target) presented on counter-phase flickering Gabor patterns (pedestal; equivalent to the superposition of two Gabors drifting in opposite directions). There were four presentation conditions. (i) Binocular: all stimuli were presented to both eyes, (ii) Monocular: all stimuli were presented to the same one eye, (iii) Dichoptic: the target was presented to one eye while the pedestal was presented to the other eye, (iv) Half-binocular: the target was presented to one eye while pedestals were presented to both eyes. In addition, we tested an increment-and-decrement condition, in which the target increased contrast for one direction of movement, but decreased it by the same amount for the opposite moving component of the pedestal. The decrement was either in the same eye as the increment, or in the other eye. Results and Discussion: Threshold-versus-pedestal-contrast (TvC) functions showed a dipper shape: thresholds decreased and then increased with pedestal contrast. At low pedestal contrasts, there was binocular summation: binocular thresholds were lower than monocular. But at high pedestal contrasts there was little difference between them. The ‘dip’ was smaller for dichoptic presentation than for other presentations. Thresholds were similar for monocular and half-binocular presentations at low pedestal contrasts, but half-binocular thresholds became higher and closer to dichoptic thresholds as pedestal contrast increased. The added decremental target lowered thresholds by about a factor of 2, compared with half-binocular, when the decrement was in the same eye as the increment, or the opposite eye. Several models fit to the data strongly suggest that motion opponency and contrast gain control operate at a binocular level of processing.

Découverte d’une fistule durale du sinus sigmoïde cliniquement caverneuse avec des signes ophtalmologiques controlatéraux : à propos d’un cas

We report the case of an 87-year-old patient who developed a dural arteriovenous fistula of the sigmoid sinus with progressive exophthalmia in the opposite eye. The patient had a unilateral decrease in visual acuity; the vessels of the conjunctiva were dilated, and a progressive central retinal vein occlusion occurred in the left eye. A dural carotid cavernous fistula of the right sigmoid sinus was diagnosed with an angiography exam and was successfully treated with embolization of the arteriovenous shunt using Onyx(®). A central partial facial nerve paralysis occurred after embolization and spontaneously resolved in 6 months. Six months after the treatment, visual acuity improved to 7/10 and the exophthalmia and central retinal vein occlusion signs regressed. Dural arteriovenous fistulae are abnormal shunts between a collateral vessel of the carotid artery and the cavernous sinus; the unilateral pulsating exophthalmia is the most frequent associated symptom. Cerebral MRI is useful to analyze indirect signs of the arteriovenous shunt showing an abnormal dilatation of the veins, but angiography of the carotid artery is essential to confirm the diagnosis. Furthermore, it allows treatment of the fistula at the same time, the main complication being the embolization of normal vessels close to the abnormal shunt. The clinical expression of the dural arteriovenous fistula on the opposite eye is infrequent and is related to the presence of complex septae within the cavernous sinus, resulting in a bilateral drainage of the cerebral venous system. The early diagnosis and management of the disease is necessary to improve the visual prognosis.

Role of Inferior Orbital Wall Morphologic Properties in Isolated Orbital Blow-Out Fracture

Purpose: To compare inferior orbital wall morphology between isolated inferior and medial orbital wall fracture patients. Methods: The morphologic properties of patients with isolated blow-out fractures involving the medial wall or inferior wall treated from August 2004 to August 2009 were reviewed. The cross-sectional area, thickness, gradient, and curvature of the inferior wall were measured via orbital CT in the opposite non-traumatized eye. Results: Patients with isolated inferior wall fractures (n = 77) and isolated medial wall fractures (n = 78) evidenced no differences in sex, age, etiology of trauma, laterality of trauma, and associated concomitant intraocular injuries. The cross-sectional area, thickness, and gradient of the inferior wall did not differ significantly between the 2 groups. However, the coefficient of curvature was significantly greater in patients with inferior wall fracture than in patients with medial wall fracture (0.016 ± 0.006 vs. 0.006 ± 0.002, respectively; p = 0.000). Conclusion: Patients with more convex and steep inferior walls are more likely to incur isolated inferior wall fractures than isolated medial wall fractures.

Spatiotemporal Brain Activity During Hiragana Word Recognition Task

The 19-channel Event-Related Potentials (ERPs) we recorded during recognition of hiragana (one type of Japanese phonetic characters) were simultaneously and independently presented as a word and a nonword to opposite eyes using a field-sequential stereoscopic 3D display with a liquid-crystal shutter, a word and a non-word were simultaneously and independently presented to the left (right) and the right (left) eyes, respectively. Each word consists of 3 hiragana characters. Three subjects were instructed to press a button when they understood the meaning of the visual stimuli after 3,000 ms poststimulus. Equivalent Current Dipole source Localization (ECDL) with 3 unconstrained ECDs was applied to the ERPs. In the case of right-handed subjects, the ECDs were localized to the Wernicke’s area at around 600 ms. In the case of left-handed subject, the ECD was localized to the Wernicke’s homologue. After that ECDs were then localized to the prefrontal area, the superior frontal gyrus, and the middle frontal gyrus. At around 800 ms, the ECDs were localized to the Broca’s area, then after that ECDs were relocalized to the the Wernicke’s area and to the Broca’s area.

Efficacy of Tetrandrine on Lowering Intraocular Pressure in Animal Model With Ocular Hypertension

To compare the efficacy of topical tetrandrine (an alkaloid isolated from the Chinese medicinal herb Radix Stephania tetrandrae S) and timolol 0.5% ophthalmic solution on lowering the intraocular pressure (IOP) in ocular normotensive and hypertensive rats. The experiment was designed as 2 parts. In the first part, normal male Sprague-Dawley rats were divided into 4 groups followed by topical administration once of 0.1%, 0.2%, 0.3% tetrandrine, and 0.5% timolol in the right eye, 0.9% saline was administered once at the opposite eye as control. In the second part, the ocular hypertension model was induced unilaterally in the rats by a diode laser treatment. Twice daily applications of the above drugs were delivered to hypertensive eyes. The control group was administered 0.9% saline. The TonoPen XL tonometer was used to determine the IOP levels. No lowering effect on IOP was detected in the normotensive rats treated with tetrandrine whereas timolol significantly reduced IOP in normotensive eyes. Both tetrandrine and timolol significantly reduced the IOP levels in the hypertensive eyes compared with the levels in the saline-treated groups. All concentrations of tetrandrine used in this study showed significant reduction of IOP in the laser-induced hypertensive eyes. Tetrandrine 0.3% had a similar efficacy as 0.5% timolol in reducing elevated IOP in ocular hypertensive eyes. This study provides evidence that tetrandrine has a major effect on lowering IOP levels in the ocular hypertension rat model. The functional mechanisms of tetrandrine require further investigation.

In vivo study comparing an X-shaped polymethylmethacrylate and a cylindrical collagen implant for deep sclerectomy

Study in vivo characteristics of a polymethylmethacrylate (PMMA) implant compared to the standard cylindrical collagen implant for deep sclerectomy (DS). Six-month comparative study. Twenty eyes of ten rabbits. Eyes were randomized to have DS with PMMA implant in one eye and collagen implant in the opposite eye. The growth of the new subconjunctival drainage vessels was assessed by combined fluorescein and indocyanin green anterior segment angiography; intrascleral and subconjunctival blebs were imaged by ultrasound biomicroscopy (UBM). At six months, outflow facility (C) was measured by anterior chamber perfusion and portions of one side of the DS were compared to portions on the 180° opposite side and native sclera on histology. The mean IOP preoperatively and at one, four, twelve, and twenty-four weeks was comparable in both groups (P > 0.1). UBM showed a statistically insignificant quicker regression of the subconjunctival bleb as well as a durable intrascleral lake in the PMMA group (P > 0.05). New drainage vessels were initially observed one month after surgery; they were more numerous in the PMMA group on angiographic and histological findings at 6 months (P < 0.05). The mean C increased significantly after surgery compared to preoperative values (P < 0.05) and no difference was observed between the implants (0.24 ± 0.06 µl/min/mmHg [PMMA] and 0.23 ± 0.07 µl/min/mmHg [collagen implant]) (P = 0.39). Deep sclerectomy performed with PMMA or collagen implants showed similar IOP lowering effects, outflow facility increase, and degree of inflammatory reaction.

Effect of topical 0.5% timolol maleate on tear production as measured by Schirmer tear test in clinically normal horses

The current study was undertaken to evaluate the effects of topical 0.5% timolol maleate on tear production in clinically normal horses. Fourteen horses free from clinically relevant ocular abnormalities were used in the study. The 14 horses were randomly assigned to a treatment or control group. The treatment group included seven horses that received 0.25 mL of 0.5% timolol maleate ophthalmic solution in a randomly chosen eye, and the opposite eye served as the untreated control. The control group included seven horses that received no topical medications during the study. Schirmer tear test was performed on both eyes of all horses 1 day prior to treatment (T0) and then at 1, 3, 7, and 14 days of treatment (T1, T3, T7, and T14). In the treatment group, the baseline (T0) Schirmer tear test (STT) values in the treated and non-treated eyes were 25.5 ± 3.8 and 26.1 ± 6.6, respectively. In the control group, baseline mean ± SD STTs were 21.4 ± 3.6 and 24.2 ± 4.4 in the right and left eyes, respectively. Baseline STTs between the treatment and control groups were not significantly different (P ≥ 0.97). There was no statistically significant change in STT values throughout the study period in treatment and control groups (P ≥ 0.15). In Conclusion, twice daily topical application of 0.5% timolol maleate had no significant effect on tear secretion when administered over a 2-week period in clinically normal horses.

Changes of Tear Film Function after Pterygium Operation

Objective: To assess changes of tear film function in patients with pterygium after pterygium excision combined with limbal-conjunctival autograft transplantation. Methods: Sixty eyes of 60 patients were entered in the study. The Schirmer test, tear breakup time (BUT) and mucus fern test (MFT) were evaluated in the patients before and after pterygium excision combined with limbal-conjunctival autograft transplantation. Results: Compared with the opposite healthy eyes, the BUT and MFT in the eyes with pterygium were significantly different before the operation (p < 0.05); however, there was no significant difference in the results of the Schirmer test (p > 0.05). The results of the BUT and MFT in the eyes with pterygium were significantly different before and 4 weeks after the operation (p < 0.05). The BUT was prolonged from 9.89 ± 3.95 to 12.78 ± 4.12 s, and the ratio of normal crystallization in the MFT increased from 46.7 to 80.0%. There was no significant difference in the Schirmer test results before and after the operation (p > 0.05). Conclusion: Tear functions were abnormal in the eyes with pterygium. Pterygium excision combined with limbal-conjunctival autograft transplantation can partially restore the tear film function into normal state, and the tear film function was stable 4 weeks after surgery.

Two presentations of nonarteritic ischemic optic neuropathy

Background Nonarteritic ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in adults over the age of 50. Patients affected notice sudden and painless loss of vision in 1 eye, often upon awaking. Studies have found that the opposite eye may be affected in approximately 15% to 20% of cases within a 5-year period. NAION vision loss results from an ischemic event often affecting the short posterior ciliary arteries. This results in optic nerve pallor, nerve fiber layer defects, and corresponding visual field defects. Case Reports Two cases of NAION are discussed here. The first patient, a 57-year-old woman, had a 10-year history of visual symptoms, and the second, a 66-year-old man, presented in less than a week after first noticing symptoms. Both had predisposing systemic risk factors and resultant visual field loss and decreased visual acuity. Conclusions Predisposing factors for NAION include small cup-to-disc ratios of the optic nerve, obstructive sleep apnea, nocturnal hypotension, diabetes, and other vascular diseases. The vision loss is irreversible, and there is no known effective treatment to prevent subsequent disc atrophy or recurring episodes.

Retinal safety of the irradiation delivered to light-adjustable intraocular lenses evaluated in a rabbit model

To evaluate the safety to the retina of a light-delivery device used to irradiate a light-adjustable intraocular lens (IOL) after implantation in a rabbit model. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. In this study, rabbits had phacoemulsification with implantation of an ultraviolet (UV)-filtering light-adjustable IOL (study IOL) in 1 eye and a custom-made silicone IOL without a UV filter (control IOL) in the opposite eye. The study IOLs were irradiated at 1.0, 2.0, 3.0, and 5.0 times the expected maximum UV irradiation doses and the control IOLs, at 0.3, 0.6, 1.0, and 2.0 times. One week after irradiation, slitlamp and fundus (indirect ophthalmoscopy) examinations were performed. The rabbits were then humanely killed and their eyes enucleated and processed for histopathology. The 16 eyes with the study IOL (with UV filter) showed no signs of corneal, anterior segment, or retinal toxicity on histopathologic evaluation. The 16 eyes with the control IOL (no UV filter) also showed no signs of corneal or anterior segment toxicity; however, 3 eyes receiving the higher radiation doses had focal areas of retinal damage consistent with laser burn. Pigmented rabbit eyes with a light-adjustable IOL with a UV filter showed no signs of retina toxicity after near-UV light exposure up to 5 times the expected maximum treatment dosage. No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Sodium orthovanadate effect on outflow facility and intraocular pressure in live monkeys

Sodium orthovanadate (Na 3VO 4) is reported to reduce IOP by affecting aqueous formation, but whether it also affects outflow facility (OF) is unclear. We tested the effect of Na 3VO 4 on OF and intraocular pressure (IOP) in live cynomolgus monkeys, and on actin and cell adhesion organization in cultured human trabecular meshwork (HTM) cells. Total OF ( n = 12) was measured by 2-level constant pressure perfusion of the monkey anterior chamber (AC) before and after exchange with 1 mM Na 3VO 4 or vehicle in opposite eyes. Topical 1% Na 3VO 4 or vehicle only was given twice daily (each 2 × 20 μL drops) for 4 days to opposite eyes ( n = 8), and Goldmann IOP was measured before and hourly after treatment for 6 h on Days 1 and 4. Filamentous actin and vinculin-containing cell adhesions were examined by epifluorescence microscopy after the cells had been incubated with 1 mM Na 3VO 4 for 24 h. A) In monkeys, Na 3VO 4 increased OF by 29.3 ± 8.8% (mean ± s.e.m.) over the perfusion interval when adjusted for baseline and contralateral eye washout ( p = 0.01; n = 12). B) Day 1 baseline IOP was 16.2 ± 1.5 mmHg in treated eyes and 15.9 ± 1.3 mmHg in the contralateral control eyes. Following treatment on Day 1, IOP was no different ( p > 0.05) between treated eyes and control eyes at any time-point or compared to baseline. Day 4 mean IOP averaged over hours 2-6 was 13.5 ± 0.8 mmHg in treated eyes and 16.1 ± 0.2 mmHg in control eyes. Treated eye IOP was lower than its Day 4 baseline ( p < 0.005), lower than control eyes for the same Day 4 interval ( p = 0.009), and lower than the Day 1 baseline ( p = 0.0000). Control eye IOP on Day 4 was not significantly different from baseline on Day 1. C) Incubation of HTM cells with 1 mM Na 3VO 4 for 24 h caused a loss of actin stress fibers and vinculin-containing adhesions. Cell retraction and separation was also observed in vanadate-treated cultures. Reformation of actin stress fibers, vinculin-containing adhesions and confluent monolayers occurred within 24 h after Na 3VO 4-containing culture medium was replaced with Na 3VO 4-free medium. Ocular administration of Na 3VO 4 to live monkeys significantly increases OF and reduces IOP. Na 3VO 4 reversibly disrupts actin and cell adhesion organization and causes retraction and separation of cultured HTM cells. Na 3VO 4 increases pressure-dependent outflow in live monkeys. Altered actin architecture in the TM may play a part in this increased OF.

Engineering the crystalline lens with a biodegradable or non-degradable scaffold

Both a biodegradable hyaluronic acid (HA) and a nondegradable polymeric gel were evaluated as scaffolds for tissue engineering the lens in Dutch Belt pigmented and New Zealand white rabbits. Following removal of the crystalline lens through a 2 mm capsulorhexis, a collagen patch or a silicone plug was placed in the capsule bag to seal the capsulotomy. In Part I, a cross-linked HA or cohesive solution of HA was injected into the capsule bag. In Part II, a synthetic polymer (SP) was injected into the capsular bag of one eye and HA followed by SP (HA/SP) was injected into the capsule bag of the opposite eye. At 3 months focal Nd:YAG laser photocoagulation was performed in an attempt to remove some retained HA gel in one eye. Overall the regenerated lenses of the HA gel groups were spherical with excellent cortical structure and clarity and a spherical nucleus of condensed HA gel. In the one eye treated with focal photocoagulation, partial clearing of the retained HA gel was noted. In the SP and HA/SP eyes, lens regrowth around the polymer was generally clear in the anterior and peripheral capsule bag and more opacified posterior to the polymeric scaffold. In summary, naturally regenerating lens tissue was directed to grow in a more normal, regular pattern by providing a biodegradable hyaluronic acid scaffold or a nondegradable polymeric optical scaffold.