Ocular Physiology Research Articles

Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats

Exogenous intake of glycotoxins present in western diet accelerates the accumulation of advanced glycation end products (AGEs) in multiple organs leading to potential tissue damage. Advanced ageing and diabetic conditions have been associated with AGEs deposition in multiple eye compartments including Bruch's membrane, optic nerve, lens and cornea. However, the impact of dietary AGEs in ocular physiology has not been extensively studied. The present study investigates the direct effects of a high AGE content diet in the ocular tissues of normal rats of different age. Two groups of baby (4 weeks of age) and adult (12 weeks of age) female Wistar rats (n = 73) were allocated to high- or low-AGE diet for 3 months. Upon completion of experimental protocol, somatometric, hormonal and biochemical parameters were evaluated in all groups. Circulating and tissue AGE levels were estimated along with their signaling receptor (receptor for AGEs, RAGE) and vascular endothelial growth factor A (VEGF-A) expression in ocular tissues of the different subgroups. High AGE intake was associated with elevated serum AGEs (p = 0.0001), fructosamine (p = 0.0004) and CRP levels (p = 0.0001) compared to low AGE. High peripheral AGE levels were positively correlated with significant increased tissue immunoreactivity of AGEs and RAGE in retinal and uveal tissues as well as retinal VEGF-A expression. Up-regulation of RAGE and VEGF-A expression was observed in the ocular tissue of both baby and adult animals fed with high-AGE diet. Co-localization of AGEs and RAGE staining was observed mainly in the inner retinal layers and the retinal pigment epithelium (RPE) of all groups. VEGF-A expression was elevated in the RPE, the inner nuclear layer and the retinal ganglion cell layer of the animals exposed to high-AGE diet. In conclusion, dietary AGEs intake affects the physiology of ocular tissues by up-regulating RAGE and VEGF-A expression contributing to enhanced inflammatory responses and pathologic neovascularization in normal organisms independent of ageing.

Proteomics of human aqueous humor.

The aqueous humor is a colorless, transparent fluid that fills the anterior chamber of the eye. It plays an important role in maintaining the intraocular pressure and providing nourishment to the lens and cornea. The constitution of the aqueous humor is controlled by the blood-aqueous barrier. Though this ocular fluid has been extensively studied, its role in ocular physiology is still not completely understood. In this study, aqueous humor samples were collected from 250 patients undergoing cataract surgery, subjected to multiple fractionation strategies and analyzed on a Fourier transform LTQ-Orbitrap Velos mass spectrometer. In all, we identified 763 proteins, of which 386 have been identified for the first time in this study. Sorbitol dehydrogenase (SORD), filensin (BFSP1), and phakinin (BFSP2) are some of the proteins that have not been previously reported in the aqueous humor. Gene Ontology analysis revealed 35% of the identified proteins to be extracellular, with a majority of them involved in cell communication and signal transduction. This study comprehensively reports 386 novel proteins that have important potential as biomarker candidates for future research into personalized medicine and diagnostics aimed towards improving visual health.

The influence of end of day silicone hydrogel daily disposable contact lens fit on ocular comfort, physiology and lens wettability

To quantify the end-of-day silicone-hydrogel daily disposable contact lens fit and its influence of on ocular comfort, physiology and lens wettability. Thirty-nine subjects (22.1±3.5 years) were randomised to wear each of 3 silicone-hydrogel daily-disposable contact lenses (narafilcon A, delefilcon A and filcon II 3), bilaterally, for one week. Lens fit was assessed objectively using a digital video slit-lamp at 8, 12 and 16h after lens insertion. Hyperaemia, non-invasive tear break-up time, tear meniscus height and comfort were also evaluated at these timepoints, while corneal and conjunctival staining were assessed on lens removal. Lens fit assessments were not different between brands (P>0.05), with the exception of the movement at blink where narafilcon A was more mobile. Overall, lag reduced but push-up speed increased from 8 to 12h (P<0.05), but remained stable from 12 to 16h (P>0.05). Movement-on-blink was unaffected by wear-time (F=0.403, P=0.670). A more mobile lens fit with one brand did not indicate that person would have a more mobile fit with another brand (r=-0.06 to 0.63). Lens fit was not correlated with comfort, ocular physiology or lens wettability (P>0.01). Among the lenses tested, objective lens fit changed between 8h and 12h of lens wear. The weak correlation in individual lens fit between brands indicates that fit is dependent on more than ocular shape. Consequently, substitution of a different lens brand with similar parameters will not necessarily provide comparable lens fit.

The analysis of measurement results of adult myopia biological optical parameters

Objective To investigate the correlations between the ocular biometric optical parameters and refractive dioptres in adults, assess the influence of the biometric optical parameters on the development of myopia, and provide a reference of prevention and treatment for myopia. Methods A total of 188 adults (376 eyes) aged 18 to 40 years old was enrolled in this study. Dioptres were measured with phoropter, A-mode ultrasound was used to measure the vitreous length and lens thickness, the axis length, anterior corneal surface semidiameter anterior chamber depth were measured with intraocular len-master (IOL-master). SPSS 17.0 software was used to analyze the date. Results ⑴ Of the 376 eyes, the results showed a statistically significant difference between myopia and emetropia in the axis length, vitreous depth, anterior corneal surface semidiameter, anterior chamber depth and lens thickness(P<0.01). ⑵ The partial correlation analysis indicated a significant positive correlation between the refraction dioptres and axial length, vitreous length (r=-0.90, -0.88, respectively, P<0.01); and significant strong correlation was also found between dioptres and anterior corneal surface horizontal and vertical semidiameter (r=0.81, 0.84, respectively, P<0.01); But correlations between dioptres and lens thickness and anterior chamber depth were very weak (r= -0.11, 0.12, respectively, P<0.01); the correlation between axial length and vitreous depth was very high (r=0.95, P<0.01). and the data indicated that the anterior corneal surface horizontal and vertical semidiameter were high positive correlation(r= 0.91, P<0.01); the same high positive correlation between the axial length and the anterior corneal surface semidiameter (horizontal/vertical) was also found (r= 0.78, 0.81, P<0.01). Conclusions Two chief factors (corneal surface semidiameter and ocular axial length) influencing the level of dioptres were high positive correlation, seeking the mutual coordination factors which promote corneal curvature change and axial growth and finding out the feedback mechanism of promoting the cornea sphericity might be conducive to further explore how to control the occurrence and development of myopia. Key words: Myopia/PP; Refraction, ocular; Eye/AH; Ocular physiology; Optics

Correction of intraocular pressure measured by Schiötz、Perkins and Rebound tonometers in rabbits by multiple regression equation

Background Rabbits are commonly used as animal models for the evaluation of drugs and surgery to lower intraocular pressure (IOP).The accuracy of IOP measurement is therefore critical in the analysis of data and subsequent extrapolation to humans.An accurate method to measure rabbit IOP is intracameral manometry,but it is an invasive way.Schiotz,Perkins and Rebound were often used in clinic.However,their accuracy in measuring rabbit IOP in experimental study is unclear. Objective The purpose of this study was to investigate the accuracy of IOP measured by Schiotz tonometer,Perkins tonometer and Rebound tonometer relative to intracameral manometry in New Zealand white rabbits. Methods The central corneal thickness (CCT),corneal curvature (CC),axial length (AL),anterior chamber depth (ACD), lens thickness (LT) and scleral thickness (ST) were respectively measured in 8 eyes of 8 healthy New Zealand white rabbits with lenstar900 and ultrasound biomicroscopy (UBM).The actual IOP was measured with a 24G needle inserted the anterior chamber and connected to a pressure transducer under the general anesthesia,the IOP gradient was set with a 24G needle inserting the vitreous cavity and connecting to a container with balanced salt solution(BSS).Then,comparative measurements at the same pressures were performed with three types of tonometers.The IOP values from Schiotz tonometer,Perkins tonometer and Rebound tonometer were calibrated based on actual IOP from intracameral manometry and eyeball physiological parameters by multiple regression equation. Results The mean of CCT,CC,AL,ACD,LT and ST was (338.96±21.52) μm,(51.68±1.66) D,(14.63±0.19) mm,(2.22±0.04) mm,(6.15±0.10) mm and (339.80±47.41) μm.Compared with the intracameral manometry value (IMV),the error range was (17.08±11.22) mmHg in the Schiotz tonometer value (STV),(25.81±12.43) mmHg in the Perkins tonometer value (PTV) and (22.50±11.47) mmHg in the Rebound tonometer value (RTV),with significant differences between them(t=10.54,14.39,13.59,all at P<0.05).Compared with IMV,the 95% limits of agreement of three portable tonometer values is larger,and three portable tonometer values had the greater measurement error with elevated IOP gradient.The regression equations was IOP=141.015+1.570×STV+0.122×CCT-3.480×CC between actual IOP and STV (R=0.92,P=0.00),IOP=-33.323+1.914×PTV+0.133×CCT between actual IOP and PTV(R=0.88,P=0.00),IOP=160.395+1.866×RTV+0.201×CCT+34.554×LT-2.649×CC+0.063×ST between actual IOP and RTV (R=0.95,P=0.00). Conclusions The physiological parameters of rabbit eyeball are obviously different from human. The STV, PTV and RTV have a great measuring error in comparson with actual IOP, and therefore it is necessary to correct STV, PTV and RTV based on the ocular physiology parameters in experimental study. Key words: Bio-measurment; Intraocular pressure; Intracameral manometry; Tonometer; Regression equation; Rabbit

End of day silicone hydrogel daily disposable contact lens fit

Purpose: To quantify the end-of-day silicone-hydrogel daily disposable contact lens fit and its influence of on ocular comfort, physiology and lens wettability. Method: Thirty-nine subjects (22.1±3.5 years) were randomised to wear each of three silicone-hydrogel daily-disposable contact lenses (narafilcon A, delefilcon A and filcon II 3), bilaterally, for oneweek. Lens fit was assessed objectively using a digital video slit-lamp at 8, 12 and 16h after lens insertion. Hyperaemia, noninvasive tearbreak-up time, tearmeniscusheight andcomfortwere also evaluated at these timepoints, while corneal and conjunctival staining were assessed on lens removal. Results: Lens fit assessments were not statistically significantly different between brands (p>0.05), with the exception of the movement at blink; narafilcon A lenses moved further on blink (0.41±0.34mm) than delefilcon A (0.33±0.21mm; p=0.030) and filcon II 3 (0.33±0.25mm; p=0.044) lenses. Overall, lag reduced from 8 to 12h (77±52% vs 69±31%; p=0.046), but remained stable from 8 to 16h (71±31%; p=0.231). Pushup recovery speed increased from 8 to 12h (0.61±0.41mm/s vs 0.76±0.47mm/s; p=0.004), but remained stable from 8 to 16h (0.73±0.40mm; p=0.621). Movement-on-blink was unaffected by wear-time (0.34±0.24mm 8h; 0.35±0.28mm 12h; 0.36±0.28mm 16h; F=0.403, p=0.670). A more mobile lens fit with one brand did not indicate that personwould have amoremobile fitwith another brand (r = 0.060.63). Lens fit was not correlated with comfort, ocular physiology or lens wettability (p>0.01). Conclusions: Among the lenses tested, objective lens fit changed between 8h and 12h of lens wear. The weak correlation in individual lens fit between brands indicates that fit is dependent on more than ocular shape. Consequently, substitution of a different lens brand with similar parameters will not necessarily provide comparable lens fit. Additional studies should be done to further assess the clinical implications of fit.

Facts and myths of cerebrospinal fluid pressure for the physiology ofthe eye.

The orbital cerebrospinal fluid pressure (CSFP) represents the true counter-pressure against the intraocular pressure (IOP) across the lamina cribrosa and is, therefore, one of the two determinants of the trans-lamina cribrosa pressure difference (TLPD). From this anatomic point of view, an elevated TLPD could be due to elevated IOP or abnormally low orbital CSFP. Both experimental and clinical studies have suggested that a low CSFP could be associated with glaucomatous optic neuropathy in normal-pressure glaucoma. These included monkey studies with an experimental long-term reduction in CSFP, and clinical retrospective and prospective studies on patients with normal-pressure glaucoma. Since the choroidal blood drains via the vortex veins through the superior ophthalmic vein into the intracranial cavernous sinus, anatomy suggests that the CSFP could influence choroidal thickness. A population-based study revealed that thicker subfoveal choroidal thickness was associated with higher CSFP. Since the central retinal vein passes through the orbital CSF space, anatomy suggests that the retinal venous pressure should be at least as high as the orbital CSFP. Other experimental, clinical or population-based studies suggested an association between higher CSFP and higher retinal venous pressure and wider retinal veins. Consequently, a higher estimated CSFP was associated with arterial hypertensive retinopathy (with respect to the dilated retinal vein diameter and higher arterial-to-venous diameter) and with the prevalence, severity and incidence of diabetic retinopathy. Physiologically, CSFP was related with higher IOP. The influence of the CSFP on the episcleral venous pressure and/or a regulation of both CSFP and IOP by a center in the dorsomedial/perifornical hypothalamus may be responsible for this. Insummary, the CSFP may be an overlooked parameter in ocular physiology and pathology. Abnormal changes in the CSFP, in particular in relationship to the IOP, may have pathophysiologic importance.

Current management approaches for uveitic glaucoma.

Uveitic glaucoma is a term that encompasses a myriad of disease entities with different etiologies, mechanisms, and prognoses. The prevalence of glaucoma in inflammatory diseases of the eye ranges from 10% to 20% in non‐population-based studies. 1‐3 The mechanisms by which intraocular inflammation causes an elevation of intraocular pressure (IOP) and subsequent secondary glaucoma vary according to the specific uveitic etiology, ocular anatomic features, ocular physiology, and treatment modalities employed which can affect eye pressure. Aqueous outflow obstruction in uveitis may be either macroscopic (ie, with synechial seclusion of the pupil, secondary pupillary block and chronic synechial, and/or neovascular angle closure) or ultrastructural (ie, with open-angle glaucoma due to microanatomic changes to aqueous outflow pathways). In acute uveitis, decreased IOP may be observed due to reduced aqueous secretion by the inflamed ciliary body (cyclitis), 4 and theoretically, facilitation of aqueous uveoscleral outflow secondary to increased aqueous concentration of prostaglandins. 5,6 Eventually, IOP may paradoxically rise secondary to increased inflammatory mediators, cells and proteins, trabecular meshwork (TM) cell dysfunction and trabeculitis, with an associated increase in resistance to trabecular aqueous outflow. 7 In addition, the prolonged use of topical corticosteroids, a mainstay of uveitis treatment, and to a lesser extent, periocular or systemic corticosteroids, may result in trabecular damage and glycosaminoglycan deposition resulting in steroid-induced glaucoma. 8‐10 The use of corticosteroid intravitreal implants in the treatment of uveitic glaucoma has also been associated with a significant elevation of IOP. 11 The corticosteroid-induced IOP rise appears to be especially pronounced in eyes where damage to the

Ocular surface anatomy and physiology underlying scleral lens application

AbstractContact lenses (CL) are in the public interest mainly for cosmetic reasons. Because of supposed simplicity of fitting, adaption, care and safety, soft CL are the predominant type world‐wide. Only few rigid gas permeable (RGB) CL are applied even though it may appear that they have less side effects. Another type of CL rests on the sclera and is hence termed scleral lenses. In contrast to the aforementioned CL, that cover only the cornea (RGB) or extend just beyond, scleral lenses have a wide diameter and cover also a large part of the bulbar conjunctiva. This leads to different impact on the anatomy, physiology and pathology of the ocular surface. Below their apex is a deep tear pond that allows to cover even major deformations of the cornea as occur in keratokonus, recurrent surface defects or scars without touching them. New sophisticated diagnostic techniques e.g. for measuring ocular surface topography as well as advanced designs and materials of standard or custom made lenses have significantly improved the fitting and the wearing comfort of scleral lenses. Therefore, scleral lenses have emerged in recent years as a new and EVER more exciting medical tool for the dedicated ocular surface specialist.

Increased intravitreal adenosine 5'-triphosphate, adenosine 5'-diphosphate and adenosine 5'-monophosphate levels in patients with proliferative diabetic retinopathy.

Extracellular purines play important role in ocular physiology, diabetes, vascular remodelling and adaptation to inflammation. This study was aimed to evaluate intravitreal purine levels in patients with diabetic retinopathy (DR) and other non-vascular vitreoretinal eye diseases. Vitreous samples were collected at the start of the three-port pars plana vitrectomy. Study group comprised 55 eyes operated due to sight-threatening forms of DR, including eyes of 24 patients with proliferative DR. Of the 143 non-diabetic controls, 112 had rhegmatogenous retinal detachment and 31 macular hole or pucker. Intravitreal purine concentrations were determined using a combination of bioluminescent [adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP)] and fluorometric [adenosine 5'-monophosphate (AMP), adenosine, inosine] enzyme-coupled sensing assays. Compared with non-diabetic controls, DR eyes contained significantly higher (p < 0.01) concentrations of ATP (4.2 ± 0.6 versus 34.5 ± 13.7 nm; mean ± SEM), ADP (19.5 ± 2.7 versus 43.7 ± 14.5 nm) and AMP (1290 ± 115 versus 1876 ± 190 nm). Intravitreal adenosine and inosine levels varied within submicromolar to low micromolar range, and their concentrations did not differ between the groups studied. High concentrations of intravitreal nucleotides ATP, ADP and AMP may be related to the pathogenesis of sight-threatening forms of DR.

Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.

Author SummarySchlemm's canal serves as a drainage tube for fluid from the anterior chamber of the eye and is directly relevant to glaucoma, a disease that causes vision loss in over 70 million people. Aqueous humor enters the canal and then drains into connected veins. Molecular understanding of the development of Schlemm's canal and its drainage functions has remained limited. We provide a detailed characterization of Schlemm's canal development, and in so doing discover a novel process of vascular development that we name “canalogenesis.” We show that although the process requires a functional KDR receptor, which is also critical in blood vessel development, the endothelial cells of Schlemm's canal have a unique hybrid molecular phenotype, expressing proteins that are characteristic of both blood and lymphatic vessels. Of note, the expression of Prox1, a master regulator of lymphatic fate, and other lymphatic proteins are largely restricted to specialized cells of the inner wall of Schlemm's canal through which the aqueous humor passes as it exits the eye. Thus, Prox1 and other lymphatic proteins may be critical for the functional specialization of these cells for aqueous humor drainage. Schlemm's canal is thus a unique vessel with a combination of blood vascular and lymphatic characteristics.

Megalin-deficiency causes high myopia, retinal pigment epithelium-macromelanosomes and abnormal development of the ciliary body in mice.

In man, mutations of the megalin-encoding gene causes the rare Donnai-Barrow/Facio-Oculo-Acoustico-Renal Syndrome, which is partially characterized by high-grade myopia. Previous studies of renal megalin function have established that megalin is crucial for conservation of renal filtered nutrients including vitamin A; however, the role of megalin in ocular physiology and development is presently unknown. Therefore, we investigate ocular megalin expression and the ocular phenotype of megalin-deficient mice. Topographical and subcellular localization of megalin as well as the ocular phenotype of megalin-deficient mice were examined with immunological techniques using light, confocal and electron microscopy. We identified megalin in the retinal pigment epithelium (RPE) and non-pigmented ciliary body epithelium (NPCBE) in normal mouse eyes. Immunocytochemical investigations furthermore showed that megalin localizes to vesicular structures in the RPE and NPCBE cells. Histological investigations of ocular mouse tissue also identified a severe myopia phenotype as well as enlarged RPE melanosomes and abnormal ciliary body development in the megalin-deficient mice. In conclusion, the complex ocular phenotype observed in the megalin-deficient mice suggests that megalin-mediated developmental abnormalities may contribute to the high myopia phenotype observed in the Donnai-Barrow Syndrome patients and, thus, that megalin harbors important roles in ocular development and physiology. Finally, our data show that megalin-deficient mice may provide a valuable model for future studies of megalin in ocular physiology and pathology.

Biocompatibility of antimicrobial melimine lenses: rabbit and human studies.

Covalent immobilization of antimicrobial peptide melimine onto contact lenses can produce broad-spectrum antimicrobial lenses. The purpose of this study was to investigate the performance of melimine-coated contact lenses in an animal model and human clinical trial. Melimine was covalently attached onto the surface of contact lenses via EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride) coupling. A rabbit model of daily contralateral wear of lenses for 22 days was conducted to assess the lens safety. A prospective, randomized, double-masked, one-day human clinical trial was used to evaluate subjective responses and ocular physiology during contralateral wear of melimine-coated (test) and uncoated (control) lenses. Delayed reactions were monitored during follow-up visits after 1 and 4 weeks. Ex vivo retention of antimicrobial activity of worn lenses was assessed by reduction in numbers of viable Pseudomonas aeruginosa and Staphylococcus aureus. Melimine-coated lenses produced no ocular signs or symptoms that would indicate cytotoxicity during the lens wear of rabbits. No histological changes were found in rabbit corneas. During the human trial, no differences were observed in wettability, surface deposition, lens-fitting centration, movement, tightness, and corneal coverage between test and control lenses (p > 0.05). There were no significant differences in bulbar, limbal, or palpebral redness or conjunctival staining (p > 0.05). Mean corneal (extent, depth, and type) staining was higher for test lenses compared with that for control lenses (p < 0.05). There was no significant difference in subjective responses for lens comfort, dryness, and awareness (p > 0.05). No delayed reactions were associated with the test lenses. Worn test lenses retained more than 1.5 log inhibition against both bacterial types. Melimine-coated contact lenses were worn safely by humans. However, they were associated with higher corneal staining. The melimine-coated lenses retained high antibacterial activity after wear.

Emerging Evidence on the Crystalline Water-Light Interface in Ophthalmology and Therapeutic Implications in Photobiomodulation: First Communication

The purpose of this study was to present preliminary evidence of the exclusion zone (EZ) and photobiomodulation (PBM) phenomena relating to ophthalmology. Water is the main media and fluid found in ocular tissues. Water is also an important photoacceptor and energy storage medium. Eyes are abundantly exposed to environmental radiant energy. Therefore, multiple light-energy-absorption mechanisms may exist, including those associated with the recently discovered fourth phase of water, known as EZ. Retrospective analysis of published data indicative of EZ phenomena related, in this first communication, to the retina and optic nerve (ON), using surgical microscopy and diffusion-weighted magnetic resonance imaging (MRI). Images showing removal of the internal limiting membrane (ILM) aided by preservative-free triamcinolone acetonide (TA) during macular hole surgery show continuous whitish lines indicative of water-layer ordering at the interface between collagen matrices and TA crystals. Apparent diffusion coefficient (ADC) results further exhibit an axis parallel to the ON, which may be an ocular expression of the EZ linked to the steady potential of the eye. Although existing results are still being decoded and analyzed in light of the state of the art studies of light-water interactions, they suggest a new understanding of the eye's bioenergetic environment, which may have deep implications in ocular physiology as well as in the pathophysiology, diagnosis, and treatment of blinding diseases using light-based therapies such as photobiomodulation. Research is needed to confirm the interpretation of these findings and validate potential ophthalmic applications.

Particularities of myopia in pregnancy

Although ocular conditions are commonly encountered in pregnancy, their management in pregnancy and during labor is still debate. Our review synthesizes the existing evidence on pregnancy and labor impact on visual outcome in myopic patients. We aimed to evaluate the changes in ocular physiology during pregnancy, the characteristics of myopia in pregnant population, the impact of epidural anesthesia and mode of delivery on myopia progression. High hormonal levels of pregnancy change corneal thickness and curvature, decrease sensitivity and reduce intraocular pressure. The existing evidence for ocular changes with pregnancy and expulsive effort in labor is rather poor. Myopic patients did not develop worsening of visual function after spontaneous vaginal delivery in any of the existing studies. Epidural anesthesia should be offered unrelated to ocular condition. Until further evidence will become available, vaginal delivery should be the standard for patients with ocular conditions in the absence of obstetrical contraindications. <br/><a href=

実験動物眼科学の基礎：生理・解剖・発生の種差

実験動物眼科学の基礎：生理・解剖・発生の種差

Vitrectomized patients: Are they at risk for glaucoma?

AbstractThe prevalence of glaucoma has been suggested to be higher in vitrectomized patients than in the overall population. The mechanisms behind this reported higher prevalence are largely unknown but literature suggests that overall ocular physiology would be impaired in vitrectomized patients. The current theories on the importance of the vitreous body in ocular oxidative stress will be discussed. Furthermore, a review of the underlying diseases needing a vitrectomy and their relationship to glaucoma will be reviewed. Practical aspects such as decision making of combining cataract surgery to vitrectomy, membrane peeling and post‐operative management of vitrectomized patients will be analyzed from the perspective of a glaucoma specialist.

Effect of Nitric Oxide on Anterior Segment Physiology in Monkeys

To determine the effect of the nitric oxide donor, sodium nitroprusside (SNP), and the nitric oxide synthase (NOS) inhibitor, L-nitro-arginine-methylester (L-NAME), on IOP, mean arterial pressure (MAP), pupil diameter (PD), refraction (Rfx), aqueous humor formation (AHF), and outflow facility (OF) in monkeys. Monkeys were treated with single or multiple topical treatments of 500 μg SNP or L-NAME to one eye. IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophotometry, and MAP with a blood pressure monitor. OF was determined by two-level constant pressure perfusion following anterior chamber exchange. Following four topical treatments with 500 μg SNP, 30 minutes apart, IOP was significantly decreased from 2 to 6 hours compared with the contralateral control with the maximum IOP reduction of 20% at 3 hours (P < 0.001). PD, Rfx, and AHF were unchanged. Effects on MAP were variable. OF after SNP exchange was significantly increased by 77% (P < 0.05) at 10(-3) M. Topical L-NAME had no effect on IOP, PD, Rfx, or MAP. Enhancement of nitric oxide concentration at targeted tissues in the anterior segment may be a useful approach for IOP reduction for glaucoma therapy. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates.

Diadenosine polyphosphates release by human corneal epithelium

Diadenosine polyphosphates are a type of dinucleotides that have been detected in rabbit and human tears. However, their origin and their mechanism of release have not been fully elucidated. In this work we investigated whether the dinucleotides Ap4A and Ap5A can be released from human corneal epithelia as a consequence of shear stress stimuli. In in vitro experiments, concentrations of Ap4A and Ap5A before mechanical stimulus of stratified human corneal epithelial cells were 3.18 ± 0.43 nM and 0.81 ± 0.13 nM, respectively. After shear stimulation, concentrations significantly increased to 12.01 ± 2.19 nM for Ap4A and 2.83 ± 0.41 nM for Ap5A. No significant differences in lactate dehydrogenase activity were detected between non-stimulated stratified human corneal epithelial cells and cells exposed to mechanical shear-stress, indicating that the rise of dinucleotide levels was not due to cell lysis. In in vivo experiments, individuals subjected to a rise in blinking frequency showed a significant increase of Ap4A (∼25-fold when experiment was performed without anaesthetic and 75-fold with anaesthetic) and Ap5A concentration in tears (∼50-fold when experiment was performed without anaesthetic and 125-fold with anaesthetic). Shear-stress stimuli induces Ap4A and Ap5A release from human corneal epithelium, thus explaining the origin of these relevant compounds for the ocular surface biochemistry and physiology.

Antioxidant delivery pathways in the anterior eye.

Tissues in the anterior segment of the eye are particular vulnerable to oxidative stress. To minimise oxidative stress, ocular tissues utilise a range of antioxidant defence systems which include nonenzymatic and enzymatic antioxidants in combination with repair and chaperone systems. However, as we age our antioxidant defence systems are overwhelmed resulting in increased oxidative stress and damage to tissues of the eye and the onset of various ocular pathologies such as corneal opacities, lens cataracts, and glaucoma. While it is well established that nonenzymatic antioxidants such as ascorbic acid and glutathione are important in protecting ocular tissues from oxidative stress, less is known about the delivery mechanisms used to accumulate these endogenous antioxidants in the different tissues of the eye. This review aims to summarise what is currently known about the antioxidant transport pathways in the anterior eye and how a deeper understanding of these transport systems with respect to ocular physiology could be used to increase antioxidant levels and delay the onset of eye diseases.