Oral 5-aminolevulinic acid combined with sodium ferrous citrate prevents blood-aqueous barrier breakdown after anterior chamber paracentesis in healthy beagle dogs.

This study investigated the preventive effect of 5-aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) on blood-aqueous barrier (BAB) breakdown induced after anterior chamber paracentesis (ACP) in beagles. 5-ALA/SFC (1/0.64 mg/kg or 3/1.92 mg/kg) or carprofen (4.0 mg/kg) was orally administered daily for 7 days prior to ACP. Then, a sample of the aqueous humor (AH) was collected from one eye via ACP (first sample) and again 60 min later (second sample). The protein and prostaglandin E2 (PGE2) concentrations in both samples were measured. Compared with the control group, high-dose 5-ALA/SFC and carprofen significantly reduced the AH protein and PGE2 concentrations in the second sample. Our findings suggest that 5-ALA/SFC suppresses BAB breakdown in dogs.

Blood-Aqueous Barrier Disruption in Penetrating and Posterior Lamellar Keratoplasty: Implications for Clinical Outcome. / Blut-Kammerwasser-Schranken-Störungen bei perforierender und posteriorer lamellärer Keratoplastik: Implikationen für das klinische Ergebnis.

BACKGROUND: The blood-aqueous barrier (BAB) separates immunoprivileged tissue of the eye from the blood circulation. Disruption of the BAB is therefore a risk factor for rejection after keratoplasty. PURPOSE: The present work provides a review of the work of our group and others on BAB disruption in penetrating and posterior lamellar keratoplasty and its implications for clinical outcome. METHODS: A PubMed literature search was performed to generate a review paper. RESULTS: Laser flare photometry provides an objective and reproducible method to assess the integrity of the BAB. Studies of the flare after penetrating and posterior lamellar keratoplasty demonstrate a mostly regressive disruption of the BAB in the postoperative course, which is influenced in extent and duration by multiple factors. Persistently elevated flare values or an increase in flare after initial postoperative regeneration may indicate an increased risk of rejection. DISCUSSION: In case of persistent or recurrent elevated flare values after keratoplasty, intensified (local) immunosuppression may potentially be useful. This could become important in the future, especially for the monitoring of patients after high-risk keratoplasty. Whether an increase of the laser flare is a reliable early indicator of an impending immune reaction after penetrating or posterior lamellar keratoplasty has to be shown in prospective studies.

Region-related and layer-specific permeability of the iris vasculature with morphological mechanism: A novel understanding of blood-aqueous barrier.

The permeability of iris blood vessels has an important role in maintaining aqueous humor (AH) homeostasis, contributing to variation in iris volume and probably the pathogenesis of angle closure glaucoma. This study investigates the permeability of the iris microvasculature to plasma-derived protein and correspond it with the morphologic characteristics of vascular mural cells (MCs). Twenty-two enucleated porcine eyes were used in this study. 12 eyes were micro-perfused with vehicle alone as control or with FITC-albumin as a marker of protein leakage and histological sections subsequently made to examine for FITC-albumin presence. The other 10 eyes were immunolabeled via micro-perfusion for αSMA and VE-cadherin to investigate their topographic distribution in the porcine iris vasculature, and to cross correspond with the locations of FITC-albumin deposits. Distribution of FITC-signals exhibited a site-dependent pattern and time-dependent change in the iris. Fluorescence was initially detected around capillaries in the superficial and deep layer of the iris microvascular network. The pupillary region and the iris root retained more fluorescent signal than the iridal ciliary region. At low magnification, αSMA labelling displayed a regional variation which was inversely correlated with vascular permeability. At the cellular level, αSMA labeling corresponded with vascular MCs distribution in the iris vascular network. The correspondence between iris microvascular permeability to FITC-albumin and the pattern of αSMA distribution and MCs coverage adds to the understanding of the elements comprising the blood-aqueous barrier with implications for the bio-mechanics of iris volume change.

Association between blood-aqueous barrier disruption and extent of retinal detachment.

PURPOSE: To investigate the association between anatomical features of rhegmatogenous retinal detachment (RRD) and the extent of blood-aqueous barrier disorder measured by non-invasiv laser flare photometry. METHODS: Retrospective evaluation of consecutive patients with RRD that underwent surgery between November 2016 and October 2018. Descriptive evaluation of pre- and postoperative parameters and correlation to preoperative laser flare value, extent of retinal detachment and re-detachment rate were performed. RESULTS: 266 patients (mean age 62.73 ± 10.40 years, 62.8% male) were included. Mean preoperative flare value was 11.0 ± 11.9 pc/ms. In pseudophakia flare values were higher than in phakia (12.7 ± 10.4 pc/ms versus 9.8 ± 12.9 pc/ms; p = 0.042). Flare increased and correlated significantly with the number of affected retinal quadrants (Q) (1 Q 6.4 ± 3.3 pc/ms; 2 Q 10.5 ± 8.8 pc/ms; 3 Q 15.6 ± 9.1 pc/ms; 4 Q 27.5 ± 33.3 pc/ms; p < 0.001; r = 0.40). Macular status correlated significantly with flare values (macula on 8.6 ± 7.1 pc/ms, off 13.1 ± 15.0 pc/ms; p = 0.004; r = 0.17). CONCLUSION: The level of objective tyndallometry in RRD seems to be influenced by lens status and extent of retinal detachment. Thus, the greater the affected retinal area is, the more blood-aqueous barrier disruption seems to be present.

Association between periodontitis and blood-ocular barrier disruption.

PURPOSE: Periodontitis causes low-grade systemic inflammation e.g., through circulatory periodontal endotoxins, and it has been associated with cardiovascular morbidity and wet age-related macular degeneration. METHODS: To assess the association between clinical severity of periodontitis and aqueous flare levels in the eyes. Patients with periodontitis (N = 15) who underwent periodontal treatment by a specialized dentist between the years 2020 and 2021 at the Chin and Mouth Disease Unit, Kymenlaakso Central Hospital, Kotka, Finland were enrolled. Aqueous flare levels, a surrogate marker for blood-aqueous and blood-retinal-barrier disruption, were measured using Laser Flare Meter (FM-600, Kowa Company, Ltd., Nagoya, Japan) before and right after the periodontal treatment and at 3 months. The number of teeth, periodontal probing depth (PPD), periodontal pathogens and antimicrobial treatment were recorded. RESULTS: At baseline, aqueous flare levels correlated with the number of clinically-relevant PPD (>5 mm) pockets (R = 0.789, P < 0.001) and inversely correlated with the number of teeth (R = -0.587, P = 0.035). At baseline, aqueous flare levels were 15.39 ± 13.24 photon units (pu)/ms among patients with periodontal pathogens, compared with 3.29 ± 1.67 pu/ms among those without any peridontal pathogens in PCR (P = 0.018). At 3 months compared to baseline values, aqueous flare levels were reduced to <50% from baseline among 6 patients (40%), whereas the levels increased to >200% from baseline in 1 patient (7%) (repeated measures ANOVA, P < 0.026). CONCLUSIONS: Poor periodontal status was associated with blood-ocular-barrier breakdown. These findings could expand our understanding of the potential mechanisms and therapeutic targets against retinal vascular diseases and systemic comorbidities in patients with periodontitis.

The Correlation of Inflammation and Microvascular Changes with Diabetic Retinal Neurodegeneration.

Purpose: To evaluate the effect of aqueous flare intensity as a measurement of inflammation and microvascular changes on retinal neurodegeneration in diabetic eyes.Materials and Methods: In cross-sectional study diabetic patients were assigned into 2 groups according to the presence of retinopathy: patients with nonproliferative diabetic retinopathy (group 1) and diabetic patients without clinically overt retinopathy (group 2). As a control group (group 3), age-matched healthy controls were included in the study. All subjects underwent visual acuity measurement, slit-lamp examination, ophthalmoscopy, spectral-domain optic coherence tomography (SD-OCT), optic coherence tomography angiography (OCTA), and laser flare-cell meter (LFCM).Results: The study enrolled 99 eyes of 99 patients in group 1; 99 eyes of 99 patients in group 2, and 50 eyes of 50 age-matched healthy controls in group 3. The eyes in group 1 had higher flare intensity, decreased ganglion cell layer (GCL) thickness, enlarged foveal avascular zone (FAZ) area, and enlarged capillary non-flow area compared to those in group 2 (p < .005). In group 1, decreased GCL thickness was statistically significantly correlated with increased aqueous flare intensity, enlarged FAZ area, and enlarged capillary non-flow area (p < .005).Conclusion: The results demonstrated a correlation of the retinal neurodegeneration with the aqueous flare levels and macular ischemia indices in the early stages of diabetic retinopathy. This finding supports the role of inflammation in the pathogenesis of diabetic retinal neuropathy.

Disruption of blood-aqueous barrier in dry eye disease.

PURPOSE: To evaluate level of flare in aqueous humor of dry eye disease (DED) and compare it with normal controls. METHODS: In this cross-sectional study, we compared the anterior chamber flare between 28 patients with DED (the DED group) and 27 normal age- and gender-matched controls (the control group). DED group was divided in SjÓ§gren's syndrome dry eye (SDE, n = 10) and non- SjÓ§gren's syndrome dry eye (non-SDE, n = 18) groups. RESULTS: This study enrolled 55 participants including 28 patients with DED and 27 normal controls. The mean age was 53.4 ± 14.7 years in the DED group and 48.5 ± 14.7 years in the control group (P = 0.086). Mean flare was significantly higher in DED group (12.1 ± 10.2 ph/ms, range 2.7-68.3) compared to the control group (5.0 ± 3.9 ph/ms, range 1.30-30.0, P < 0.001). There was no statistically significant difference in the flare intensity between the SjÓ§gren syndrome dry eye (SDE) group (14.5 ± 14.4 ph/ms) and the non-SjÓ§gren dry eye (non-SDE) group (10.8 ± 6.9 ph/ms, P = 0.330). A significant correlation was observed between the flare intensity and the ocular surface staining in the SDE group (r = 0.62, P = 0.018). CONCLUSION: There is a significant increase in aqueous humor flare in patients with DED. Such finding, which is a marker of disruption of blood-aqueous barrier, demonstrates deeper tissue involvement than ocular surface in these patients.

Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study.

BACKGROUND: This study aims to use laser flare photometry to evaluate flare changes in patients following corneal damage from a metallic foreign body (FB). METHODS: Foreign body injured eyes and the healthy fellow eyes of 54 consecutive patients were studied in this comparative, observational, cross-sectional study. Flare levels were analyzed according to demographics, history of previous exposures, foreign body location, and foreign body penetration into the injured cornea. RESULTS: The mean flare value was significantly higher for the eyes with corneal foreign body injury compared to the fellow-control eyes (11.35±14.17 ph/ms and 6.30±3.81 ph/ms, respectively) (p=0.014). The mean flare values were significantly lower in eyes with a history of more than one previous corneal foreign body removal flare values than in other eyes (p=0.029). CONCLUSION: Flare is increased by corneal foreign body exposure. However, eyes that experience multiple previous corneal foreign body exposures may show relatively low flare, probably due to corneal desensitization.

Comparison of topically administered 0.05% difluprednate and 1% prednisolone acetate for inhibition of aqueocentesis-induced breakdown of the blood-aqueous barrier in healthy dogs.

OBJECTIVE: To compare the efficacy of 0.05% difluprednate ophthalmic emulsion and 1% prednisolone acetate ophthalmic suspension for controlling aqueocentesis-induced breakdown of the blood-aqueous barrier in healthy dogs. ANIMALS: 34 healthy dogs. PROCEDURES: Dogs were allocated to 5 groups (6 to 8 dogs/group) to receive 0.05% difluprednate, 1% prednisolone acetate, or saline (0.9% NaCl) solution (control treatment) in both eyes 2 or 4 times daily. Eye drops were administered topically for 5 consecutive days. Anterior chamber paracentesis (aqueocentesis) was performed in 1 eye on the third day. Automated fluorophotometry was performed immediately before and 20 minutes and 24 and 48 hours after aqueocentesis. Relative fluorescence (RF), defined as fluorescence of the eye that had undergone aqueocentesis divided by fluorescence of the contralateral eye, was calculated to help control for variation among dogs. RESULTS: Mean RF was significantly lower at 24 hours after aqueocentesis in dogs treated twice daily with 0.05% difluprednate or 4 times daily with 1% prednisolone acetate than in dogs receiving the control treatment. At 48 hours after aqueocentesis, mean RF was significantly lower in dogs treated 4 times daily with 1% prednisolone acetate than in control dogs. Mean RF differed over time in dogs treated 4 times daily with 0.05% difluprednate but did not differ over time for any of the other treatments. CONCLUSIONS AND CLINICAL RELEVANCE: All 4 treatments were effective for reducing aqueocentesis-induced anterior uveitis in healthy dogs regardless of the drug or frequency of administration. Topical ophthalmic administration of 0.05% difluprednate may be a viable treatment option for dogs with anterior uveitis and warrants further study.

Effect of Tropicamide on Laser Flare Meter Measurements in Patients with Pseudoexfoliation.

PURPOSE: To investigate the effect of 1% tropicamide on anterior chamber aqueous flare (ACAF) measurements acquired with laser flare meter in patients with pseudoexfoliation. METHODS: Thirty-three eyes of 33 patients with pseudoexfoliation were enrolled. Patients with the history of other ocular diseases, intraocular surgeries, and the presence of severe posterior synechia were excluded. Besides routine ophthalmological examination, ACAF levels were measured by laser flare meter device (Kowa FM 600) before and after instillation of 1% tropicamide. RESULTS: The mean age of 33 patients was 67.3±7.1 (53-85) years. Patients had a mean best corrected visual acuity of 0.25±0.41 (1.80-0.00) logMAR, cup-to-disc ratio of 0.45±0.22 (0.2-1), and IOP of 15.33±2.82 (9-20) mmHg. Although the mean ACAF value increased from 14.68±8.40 (3.4-40.4) photon/ms predilation to 15.41±10.74 (3.8-46.8) photon/ms post-dilation, the difference was not statistically significant (p=0.835). CONCLUSIONS: ACAF values in patients with pseudoexfoliation did not significantly differ after instillation of 1% tropicamide.

Nanoscale delivery systems in treatment of posterior ocular neovascularization: strategies and potential applications.

Pathologic posterior neovascularization of eye is a major cause of irreversible vision loss and limitations of therapeutics to be successfully delivered to back of the eye has been a main obstacle for its effective treatment. Current pharmacological treatment using anti-VEGF agents being delivered intravitreally are effective but complicated due to anatomical and physiological barriers, as well as administration of high and frequent doses. With expanding horizons of nanotechnology, it can be possible to formulate promising nanoscale delivery system to improve penetration and sustained the release of therapeutic in posterior segment of the eye. Taking into consideration advances in the field of nanoscale delivery systems, this special report focuses on emerging strategies and their applications for treatment of posterior ocular neovascularization.

Breakdown of the blood-eye barrier in choroidal melanoma after proton beam radiotherapy.

PURPOSE: Irradiation of choroidal melanoma is a safe and globe preserving procedure. Chronic inflammatory processes and ischemia are the main reasons for secondary enucleation in the long run. The aim of this study was to determine whether intraocular inflammation and especially inflammatory response after proton beam therapy (PBT) is related to primary tumor characteristics such as height, tumor volume, and initial flare values. METHODS: Twenty-six patients treated for uveal melanoma using PBT were included. All patients were examined for signs of inflammation using laser flare photometry (LFP). Each examination included assessment of the melanoma and fellow eye (which acted as the control) and imaging of the melanoma. RESULTS: Significant differences of flare values between melanoma eyes and control group were found both at baseline (median 17.65 ph/ms (min 4, max 37.10), 7.45 ph/ms (min 0.80, max 16.40), respectively) and during follow-up (median 21.45 ph/ms (min 4.5, max 70.90); 6.05 ph/ms (min 2.40, max 16.40), respectively) (p < 0.001, Wilcoxon test). Flare values in melanoma eyes increased significantly after PBT (p = 0.005, Wilcoxon test) and after a follow-up of 94 days (median, 7-420 days). Flare values of the control group did not change (p = 0.946, Wilcoxon test). The increase of flare values correlated significantly with maximum tumor height and volume (Spearman-Rho 0.633, p = 0.001 and 0.519, p = 0.007, respectively). CONCLUSION: LFP has proven to show significantly higher flare values in melanoma eyes as compared with the control group and provides data on the course of the inflammatory response after treatment. It may ease treatment planning both at baseline and during follow-up.

The Effect of Molecular Weight on Passage of Proteins Through the Blood-Aqueous Barrier.

Purpose: To determine the effect of molecular weight (MW) on the concentration of plasma-derived proteins in aqueous humor and to estimate the plasma-derived and eye-derived fractions for each protein. Methods: Aqueous humor and plasma samples were obtained during cataract surgery on an institutional review board-approved protocol. Protein concentrations were determined by ELISA and quantitative antibody microarrays. A total of 93 proteins were studied, with most proteins analyzed using 27 to 116 aqueous and 6 to 30 plasma samples. Results: Plasma proteins without evidence of intraocular expression by sequence tags were used to fit a logarithmic model relating aqueous-plasma ratio (AH:PL) to MW. The log(AH:PL) appears to be well predicted by the log(MW) (P < 0.0001), with smaller proteins such as cystatin C (13 kDa) having a higher AH:PL (1:6) than larger proteins such as albumin (66 kDa, 1:300) and complement component 5 (188 kDa, 1:2500). The logarithmic model was used to calculate the eye-derived intraocular fraction (IOF) for each protein. Based on the IOF, 66 proteins could be categorized as plasma-derived (IOF<20), whereas 10 proteins were primarily derived from eye tissue (IOF >80), and 17 proteins had contribution from both plasma and eye tissue (IOF 20-80). Conclusions: Protein concentration of plasma-derived proteins in aqueous is nonlinearly dependent on MW in favor of smaller proteins. Our study demonstrates that for proper interpretation of results, proteomic studies evaluating changes in aqueous humor protein levels should take into account the plasma and eye-derived fractions.

Comparison of early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on the ocular inflammatory response induced by paracentesis in healthy canine eyes.

OBJECTIVE: We investigated the early posttreatment effects of two steroidal anti-inflammatory ophthalmic drugs on blood-aqueous barrier (BAB) breakdown by paracentesis in dogs. ANIMAL STUDIES: We studied 21 healthy beagles with normal eyes. PROCEDURES: Controlled anterior chamber paracentesis (0.5 mL) was performed in one eye of each dog. Control group dogs (n = 7) received no medication, whereas those in the treatment groups received a topical anti-inflammatory medication (difluprednate [DFBA] ophthalmic emulsion 0.05% [n = 7] or betamethasone [BMZ] sodium phosphate ophthalmic solution 0.1% [n = 7]) at 0, 15, 30, and 45 minutes after initial paracentesis in the paracentesed eyes. Secondary aqueous humor (AH) was collected 60 minutes after initial paracentesis. Protein and prostaglandin E2 (PGE2 ) concentrations in AH were determined using the bicinchoninic acid assay and commercially available immunoassay kit, respectively. All mean values in the three groups were compared using analysis of variance followed by Tukey's post hoc test. RESULTS: Aqueous protein and PGE2 concentrations were markedly increased at 60 minutes following paracentesis. Both concentrations in the secondary AH of the DFBA group were significantly lower than those of the control group; however, treatment with BMZ had no significant effects. CONCLUSIONS: Early postparacentesis treatment with DFBA was more effective than that with BMZ for reducing aqueous protein and PGE2 contents in dogs with paracentesis-induced BAB breakdown. DFBA may be an appropriate treatment during the early stage of anterior uveitis caused by intraocular surgery in dogs.

Application of Laser Flare Photometry in the Quantification of Blood-Aqueous Barrier Breakdown after Micro-incision Vitrectomy.

Purpose: The purpose of the study is to quantify aqueous flare using laser flare photometry (LFM) in patients undergoing 25-G pars plana vitrectomy (PPV) and assess the need for postoperative topical corticosteroid administration . Methods: Prospective evaluation of 50 eyes (50 patients) was performed using LFM until day 30 postoperative. Duration of surgery, indication of PPV, and use of laser and/or cryotherapy were noted. Topical corticosteroids were used if mean LFM values were >50, or if there was anterior chamber fibrin. Results: Mean age of the subjects was 48.62 ± 10.07 years. The preoperative LFM value for 50 subjects was 17.42 ± 25.20. Topical corticosteroids were initiated in only 22 patients. The LFM values of subjects were not different from baseline at 1 month whether or not the subjects received corticosteroids (p > 0.106). Conclusions: With 25-G PPV, there is minimal breakdown of blood-aqueous barrier. LFM helps in monitoring postoperative inflammation, obviating the need for topical corticosteroids in significant number of patients.

Effect of oral administration of robenacoxib on inhibition of paracentesis-induced blood-aqueous barrier breakdown in healthy cats.

OBJECTIVE To determine the effect of oral administration of robenacoxib on inhibition of anterior chamber paracentesis (ACP)-induced breakdown of the blood-aqueous barrier (BAB) and assess whether robenacoxib can cross an intact BAB in healthy cats. ANIMALS 12 healthy adult domestic shorthair cats. PROCEDURES Cats received robenacoxib (6-mg tablet in a treat, PO; n = 6) or a control treatment (treat without any drug, PO; 6) once daily for 3 days, beginning 1 day before ACP. One eye of each cat served as an untreated control, whereas the other underwent ACP, during which a 30-gauge needle was used to aspirate 100 µL of aqueous humor for determination of robenacoxib concentration. Both eyes of each cat underwent anterior chamber fluorophotometry at 0 (immediately before), 6, 24, and 48 hours after ACP. Fluorescein concentration and percentage fluorescein increase were used to assess extent of ACP-induced BAB breakdown and compared between cats that did and did not receive robenacoxib. RESULTS Extent of BAB breakdown induced by ACP did not differ significantly between cats that did and did not receive robenacoxib. Low concentrations of robenacoxib were detected in the aqueous humor (mean, 5.32 ng/mL; range, 0.9 to 16 ng/mL) for 5 of the 6 cats that received the drug. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of robenacoxib did not significantly decrease extent of BAB breakdown in healthy cats. Detection of low robenacoxib concentrations in the aqueous humor for most treated cats indicated that the drug can cross an intact BAB.

Does the disruption of horizontal anterior ciliary vessels affect the blood-aqueous barrier function?

PURPOSE: To investigate the significance of the anterior ciliary vessels (ACVs) preservation during the conventional horizontal strabismus surgery. METHODS: Patients (≥ 8 years) with horizontal strabismus were randomly allocated into group 1 (with ACV preservation) and group 2 (without ACV preservation). The surgical eyes in group 1 were further divided into group A (one rectus muscle operated) and group B (two rectus muscles operated). Similarly, eyes in group 2 were divided into group C (one rectus muscle operated) and group D (two rectus muscles operated). The success rate of ACV preservation was calculated. The anterior chamber flare measurements of each eye by laser flare photometry were recorded on the day prior to and after operation. The flare values between groups and between pre- and post-operation in each group were compared by one-way analysis of variance and a paired t-test respectively. RESULTS: In groups A and B, the success rate of ACV preservation was 82% (27/33) and 70% (28/40)respectively, and the flare values between pre- and post-operation showed no significant differences(4.378 ± 1.527, 4.544 ± 1.452, P = 0.526; 4.625 ± 1.090, 4.989 ± 1.468, P = 0.101 respectively). However, the postoperative values were significantly increased in group C and group D(4.661 ± 1.031, 5.039 ± 1.310, P = 0.025; 4.933 ± 1.691, 5.502 ± 1.430, P = 0.000 respectively). The postoperative flare readings of group D were significantly higher than group B, while group A and group C had no significant variation. CONCLUSION: ACV preservation probably has clinical significance in reducing the undesirable influence on the blood-aqueous barrier.

Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology.

Drug Delivery to the Posterior Segment of the Eye.

Drug delivery into the posterior segment of the eye is complicated by the existence of the blood-ocular barrier. Strategies for delivering drugs to the posterior segment include systemic administration, modification of the barrier, and local drug delivery (including transcorneal, transscleral, and intravitreal). The most commonly used method for drug delivery into the posterior segment is by intravitreal injection. Other routes that can be used to achieve therapeutic drug levels in the posterior segment include topical, iontophoretic, and juxtascleral delivery. Extended-release intravitreal drug delivery systems can achieve sustained therapeutic levels with the goal of providing a prolonged clinical benefit with significantly fewer interventions.