Macular function and morphology in acute retinal pigment epithelitis

A 20-year-old man applied with vision loss in the left eye. Right eye examination was unremarkable. Best-corrected visual acuity (BCVA) in the left eye was 20/200. Fundus examination revealed a few yellow spots within a round-shaped macular lesion. Autofluorescence imaging showed hyperautofluorescence in the lesion. Central amplitudes in multifocal electroretinogram (mfERG) were depressed. The patient reported a rhinopharyngitis 7–10 days before the visual loss. The patient was diagnosed as acute retinal pigment epithelitis. BCVA improved gradually up to 20/20 in 4 weeks. mfERG amplitudes returned to normal. A slight pigmentary distortion was the only residual fundus finding.     

蓝光照射对小鼠视网膜形态和功能的损伤作用

目的通过观察蓝光照射对C57BL/6J小鼠视网膜形态和功能的影响,探讨非渗出性年龄相关性黄斑变性(AMD)的模型。方法采用投币法将20只8周龄清洁级C57BL/6J雄性小鼠随机分为正常对照组和蓝光照射组。蓝光照射组小鼠暗适应24 h后暴露于10000 lx蓝光下5 d,正常对照组小鼠按12 h/12 h正常光照/黑暗的周期饲养于正常光照环境5 d。采用光相干断层扫描成像(OCT)活体检查各组小鼠视网膜厚度变化,采用视网膜电图(ERG)检查各组小鼠视网膜功能变化。于光照结束后24 h采用颈椎脱臼法处死小鼠并制备眼球壁标本,采用免疫荧光染色法测定小鼠视网膜中视紫红质(Rho)、紧密连接蛋白(ZO-1)和β-catenin蛋白表达。结果蓝光照射组小鼠视网膜上部和下部距视盘200、400、600、800和1000μm处视网膜外核层厚度均较正常对照组变薄,差异均有统计学意义(均P<0.05)。蓝光照射组小鼠暗适应和明适应b波振幅分别为(305.50±41.52)μV和(119.50±6.67)μV,分别低于正常对照组的(415.50±28.77)μV和(139.75±8.26)μV,差异均有统计学意义(均P<0.05)。正常对照组小鼠RPE细胞呈正六边形,视网膜各层形态规则,Rho、ZO-1和β-catenin荧光较强;蓝光照射组小鼠RPE细胞形态不规则,ZO-1染色减弱或消失,β-catenin染色和Rho蛋白荧光强度减弱。结论蓝光照射小鼠视网膜变薄,视网膜功能减弱。     

视网膜脱离复位后视功能研究

目的 研究视网膜脱离（ＲＤ）术后视功能的恢复及其影响因素。方法 选择孔源性ＲＤ痊愈病例２３３例（２３８眼）,采用Ｘ＾２检验进行统计分析。结果 术前３６．７％患者视力≥０．１,而术后为８１．４％（Ｐ〈０．０１）;术前黄斑不脱离和脱离１周内的患者术后视力１００．０％≥０．３,脱离１周后只有２７．１％的患者有相应的视力;术前视力与术后视力明显相关（r＝０．５１７,Ｐ〈０．０１）。结论 ＲＤ术后视力得到不     

Outcomes of primary rhegmatogenous retinal detachment in myopes of five or more diopters

OBJECTIVE: To analyze surgical outcomes of primary rhegmatogenous retinal detachment in high myopes. MATERIALS AND METHODS: Medical records of 201 patients who underwent vitreoretinal surgeries for primary retinal detachments were reviewed. Fifty-two eyes of 51 patients with at least 5.00 diopters (D) of myopia were included. RESULTS: The mean refractive error was -9.8+/-5.4 D (mean +/- SD). Macula was off in 29 (55.8%) eyes. Thirty-six (69.2%) and 16 (30.8%) eyes received scleral buckling (SB) and pars plana vitrectomy (PPV), respectively. Primary anatomical success rate was 86.1% and 75.0% in the SB and PPV group, respectively. The anatomical success rate after 2 operations was 94.4% and 100% in the SB and PPV group, respectively. Twenty-three (63.1%) patients from SB group and 10 (62.5%) patients from PPV group attained postoperative best-corrected visual acuity of 20/60 or better. CONCLUSION: The anatomical and visual outcomes of primary rhegmatogenous retinal detachment in myopes of five or more diopters seem favorable after surgery.     

卵磷脂络合碘对视网膜脱离复位术后低视力患者视网膜功能和形态的影响

目的探讨卵磷脂络合碘对视网膜脱离（RD）术后视网膜功能和黄斑部视网膜形态的干预效果。方法采用前瞻随机对照研究的方法将50例（50眼）RD术后患者分为卵磷脂络合碘组和对照组；应用视网膜电图（ERG）和光学相干断层扫描（OCT）方法观察术后1、2、4、8周视网膜功能和形态的改变。结果对照组和用药组的年龄、视力和病程匹配。与术后第1周ERGb波比较，用药组第2周ERGb波即有显著的改变，而对照组延迟到第8周。OCT检查表明，用药组黄斑部视网膜厚度在术后第4周明显改善，而对照组为术后第8周。术后第8周用药组患者的最佳矫正视力与对照组的差异有统计学意义（P〈0．01）。结论卵磷脂络合碘可在一定程度上促进RD术后视功能的改变。     

In vivo quantitation of autofluorescence in human retinal pigment epithelium

We measured autofluorescence of the macula with fluorophotometry to evaluate age-related changes in human retinal pigment epithelium. Examined in this study were 35 aphakic eyes of 25 patients, ranging in age from 52 to 87 years, after uneventful intracapsular cataract extraction and 21 normal phakic eyes of 20 patients, ranging in age from 9 to 29 years. Autofluorescence at the macula of aphakic eyes increased in an age-dependent manner (r = 0.514; p less than 0.01) as follows: 15.0 ngEq/ml for the sixth decade (n = 1), 17.2 +/- 4.2 for the seventh decade (n = 11), 21.3 +/- 3.6 for the eighth decade (n = 16) and 24.6 +/- 2.7 for the ninth decade (n = 7). We believe that the autofluorescence originates mainly from lipofuscin in the retinal pigment epithelium, and that the autofluorescence enhanced with age reflects the accumulation of lipofuscin.     

青少年近视患者夜戴角膜塑形镜后的视觉质量评估

背景角膜塑形镜配戴可暂时改变眼的近视度数,但其对配戴者视觉质量的影响值得关注。目的观察青少年近视患者使用夜戴型角膜塑形镜后视觉质量的改变。方法采用描述性系列病例观察研究设计。每个受试者纳入研究前均签署知情同意书。收集2010年1月1日至12月30目的近视患者76例150眼,年龄（14．90-＋1．24）岁;平均等效球镜度（SE）为（-2．79＋0．82）D。所有患者均在四川大学华西医院眼科配戴夜用型角膜塑形镜,每日戴镜至少8h,分别于配戴前及配戴后第1周、第3个月时接受主觉验光、裸眼视力（UCVA）、对比敏感度、角膜地形图、像差检查,并由同一验配医师询问患者配戴前后的视觉质量及相关症状。视觉质量的评价标准参照美国国家眼科研究院屈光不正生活质量量表（NEI—RQL42）,采用SPSS13．0统计学软件对相关数据进行重复测试单因素方差分析。结果配戴角膜塑形镜1周、3个月后sE分别为（-0．33±1．02）D和（-0．26±0．60）D,较配戴前的（-2．79±0．82）D显著下降,差异均有统计学意义（P〈0．01）,而配戴后1周和3个月问sE差异无统计学意义（P=0．161）。配戴角膜塑形镜后1周和3个月各空间频率下对比敏感度均低于配戴前,差异均有统计学意义（1周：3cpd时P=0．001,6cpd时P=0．001,12cpd时P〈0．05,18cpd时P〈0．05;3个月：3cpd时P=0．001,6cpd时P=0．001,12cpd时P〈0．05,18cpd时P〈0．05）,而配戴后1周和3个月之间患眼对比敏感度的差异均无统计学意义（P〉0．05）。配戴角膜塑形镜1周、3个月后角膜平坦K值、陡峭K值、e值均较配戴前明显降低,差异均有统计学意义（均P=0．000）,而角膜表面非对称指数（SAI）、角膜表面规则指数（SRI）较配戴镜前均明显增加,差异均有统计学意义（均P=0．001）。配戴角膜塑形镜前后的像差研究显示,总高阶像差、3阶像差和4阶像差在戴镜后1周和3个月均明显增加,与戴镜前比较差异有统计学意义（P〈0．05）,戴镜后1周和3个月间差异均无统计学意义（P〉0．05）,总像差及2阶像差在戴镜1周后与3个月均显示降低,与戴镜前比较差异均有统计学意义（P〈0．05）,但戴镜后1周和3个月间差异均无统计学意义（P〉0．05）。配戴角膜塑形镜前后5项视觉质量项目（从明处到暗处适应容易程度、夜间骑车容易程度、夜间是否常看到灯光晕环光圈、视力波动出现的频率、眩光程度）评分的差异均有统计学意义（P〈0．05）,而视力波动出现的频率在配戴后1个月和3个月间差异均有统计学意义（P〈0．05）。结论配戴夜戴型角膜塑形镜戴后1周可使近视度数降低,配戴3个月近视度数趋于稳定。配戴角膜塑形镜可使角膜形状趋向不规则,对比敏感度下降,3阶像差和4阶像差增加。主观视觉质量较框架眼镜矫正时降低,尤其是夜间视觉质量。     

房水流出通道形态及功能在体评估进展

青光眼病理性高眼压的常见原因是房水流出受阻,因此房水流出通道的形态观察和功能研究是青光眼防治的重点。研究房水流出通道的形态及功能对研究青光眼发病机制、选择手术方式和开发靶向药物均有重要意义。房水流出成像方式中眼前段相干光断层扫描及血管成像、超声生物显微镜活体显像,可对房水流出通道进行结构性评估;而静态和实时房水血管造影为功能性评估。目前尚缺乏房水结构流出特征与功能流量值之间的精确关系研究。使用房水血管造影术可研究与评价青光眼的药物疗效。房水血管造影术有助于引导小梁网靶向的微创青光眼手术以获得更好的降眼压效果。但房水血管造影术有创,目前只能在手术室使用。未来尚需进一步改进评估房水流出通道的方法,以期在临床上通过结构和功能评估相结合,更好地了解房水流出通道和眼前段结构,提高青光眼诊治水平。（国际眼科纵览,2020, 45：397-403）     

The development of scotopic retinal function in human infants

Scotopic retinal function undergoes age-related changes early in human infancy. Electroretinographic, psychophysical, and pupillographic responses have been used in the study of normal development. Various components of the electroretinographic responses index distal and proximal retinal function. Changes in pupillary diameter, measurable in infants under carefully selected conditions, represent rhodopsin regeneration in the photoreceptor outer segment. From psychophysical data, inferences can be drawn about scotopic retinal control of visual performance. These data constrain theories about the determinants of sensitivity, about the flow of signals from the distal, rhodopsin-bearing, outer segments to the proximal retina, and about modulations of straight-through flow by feedback or inhibitory circuits. The results indicate that the post natal development of human scotopic function is due mainly to reorganization of processes central to the photoreceptors.     

Effects of patent blue on human retinal function

Background Dye solutions for intraoperative staining of epiretinal membranes and the internal limiting membrane improve the visualisation of these thin structures and facilitate their removal. Lately, the application of patent blue for staining of the internal limiting membrane has been proposed as an alternative to the standard procedures during macular hole surgery. In the present study we investigated the effects of patent blue 0.48% on human retinal function.Methods An isolated human retina preparation was perfused with a standard solution and the electroretinogram (ERG) was recorded repeatedly. After recording of stable ERG amplitudes the nutrient solution was substituted by a commercially available patent blue solution. The duration of retinal exposure to the dye solution was varied between 15 s and 4 min. Thereupon, the preparation was reperfused with standard solution for 2 h. The percentage of b-wave reduction after exposition was calculated.Results No effects on the human ERG were seen after 15 and 30 s of dye application. Reversible reductions of the b-wave amplitude were found for an exposure period of 60 and 120 s, respectively. After 4 min of patent blue application a persistant b-wave amplitude reduction by 40% was found.Conclusions Patent blue affects human retinal function when applied for at least 1 min. However, no irreversible effects on the human ERG were seen even after 2 min of retinal exposure to patent blue. Thus, toxic effects on retinal function after intraoperative short-term application of patent blue 0.48% appear unlikely to occur.Presented in part during the Annual Congress of the German Ophthalmological Society (DOG) in Berlin, 2004     

Cognition, ocular accommodation, and cardiovascular function in emmetropes and late-onset myopes

PURPOSE: To investigate objectively and noninvasively the role of cognitive demand on autonomic control of systemic cardiovascular and ocular accommodative responses in emmetropes and myopes of late-onset. METHODS: Sixteen subjects (10 men, 6 women) aged between 18 and 34 years (mean +/- SD: 22.6 +/- 4.4 years), eight emmetropes (EMMs; mean spherical equivalent [MSE] refractive error +/- SD: 0.05 +/- 0.24 D) and eight with late-onset myopia (LOMs; MSE +/- SD: -3.66 +/- 2.31 D) participated in the study. Subjects viewed stationary numerical digits monocularly within a Badal optical system (at both 0.0 and -3.0 D) while performing a two-alternative, forced-choice paradigm that matched cognitive loading across subjects. Five individually matched cognitive levels of increasing difficulty were used in random order for each subject. Five 20-second, continuous-objective recordings of the accommodative response measured with an open-view infrared autorefractor were obtained for each cognitive level, whereas simultaneous measurement of heart rate was continuously recorded with a finger-mounted piezoelectric pulse transducer for 5 minutes. Fast Fourier transformation of cardiovascular function allowed the relative power of the autonomic components to be assessed in the frequency domain, whereas heart period gave an indication of the time-domain response. RESULTS: Increasing the cognitive demand led to a significant reduction in the accommodative response in all subjects (0.0 D: by -0.35 +/- 0.33 D; -3.0 D: by -0.31 +/- 0.40 D, P < 0.001). The greater lag of LOMs compared with EMMs was not significant (P = 0.07) at both distance (0.38 +/- 0.35 D) and near (0.14 +/- 0.42 D). Mean heart period reduced with increasing levels of workload (P < 0.0005). LOMs exhibited a relative elevation in sympathetic system activity compared to EMMs. Within refractive groups, however, accommodative shifts with increasing cognition correlated with parasympathetic activity (r = 0.99, P < 0.001), more than with sympathetic activity (r = 0.62, P > 0.05). CONCLUSIONS: In an equivalent workload paradigm, increasing cognitive demand caused a reduction in accommodative response that was attributable principally to a concurrent reduction in the relative power of the parasympathetic component of the autonomic nervous system (ANS). The disparity in accommodative response between EMMs and LOMs, however, appears to be augmented by changes in the sympathetic nervous component of the systemic ANS.     

影响视网膜脱离患者视网膜功能的因素

目的:评价视网膜脱离患者年龄、病程、视网膜脱离面积、黄斑脱离情况等因素对视网膜功能的影响。方法:将孔源性视网膜脱离(retinal detachment,RD)188例189眼的患者年龄、病程、视网膜脱离面积、黄斑脱离情况、视力与视网膜脱离眼的fERG和mfERG各指标进行相关分析。结果:影响RD眼fERG和mfERG的主要因素是脱离面积、黄斑脱离和视力。以|γ|>0.4,且P≤0.05判定为有相关性。脱离面积与明视和暗适应最大反应ERG a、b波幅值,30Hz闪烁光幅值,OPs波数和幅值负相关;与mfERG象限野P1波幅值密度、幅值负相关。相关系数最高者为fERG暗适应最大反应b波幅值(γ=-0.704)。黄斑脱离与明视和暗适应最大反应ERG b波幅值,30Hz闪烁光ERG幅值负相关;与mfERG环形野环1的P1波幅值密度、幅值负相关,与mfERG象限野P1波幅值密度负相关,相关系数最高者为mfERG环形野环1的P1波幅值(γ=-0.584)。视力与明视和暗适应最大反应a、b波幅值,30Hz闪烁光幅值,OPs子波数和幅值正相关;与mfERG环形野环1的P1波幅值密度、幅值正相关,相关系数最高者为30Hz闪烁光ERG幅值(γ=0.597)。RD眼的fERG异常率最高者为暗适应最大反应ERG b波幅值,异常率为71.3%,视网膜脱离象限野mfERG异常率最高者为P1波幅值,异常率为85.3%。结论:影响RD患者视网膜功能的重要因素是脱离面积和黄斑脱离情况。RD眼对视网膜功能异常反应的mfERG对视网膜功能异常反应的敏感性高于fERG。     

Acute hypoglycemia decreases central retinal function in the human eye

The goal of this pilot study was to assess the effects of acute hypoglycemia on retinal function and contrast sensitivity in individuals with and without diabetes. Hyperinsulinemic hypoglycemic and euglycemic clamp procedures were performed in subjects without diabetes (n = 7) and with controlled type 1 diabetes (n = 5). Mean age was 28 years, and none had retinal disease. During euglycemia (glucose 95-110 mg/dl) and acute hypoglycemia (glucose 50-55 mg/dl), contrast sensitivity was measured and spatial retinal responses were recorded with multifocal electroretinograms (mfERG), a rapid technique for mapping sensitivity from the foveal, macular and peripheral areas of the retina. During hypoglycemia, retinal responses (mfERG P1 wave) were decreased in both type 1 diabetes subjects and subjects without diabetes. The dominant effect was in the amplitude of the responses in the central macular retina, not in their temporal properties. Responses from the central region, central 10⁰, were on average 1.8-fold lower than those from the periphery for both groups. All diabetes subjects and 3/7 without diabetes reported central scotoma. Decreases in mfERG amplitude were accompanied by decreases in contrast sensitivity. These changes were immediately reversed with the restoration of euglycemia. Overall, this study demonstrates that the acute effects of hypoglycemia in the human eye predominantly involve central vision, and these visual effects originate, at least in part, in the retina. The association between low blood glucose levels and impaired central vision underscores the importance of avoiding when possible and promptly treating hypoglycemia, particularly in individuals with diabetes.     

In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function

PURPOSE: To relate in vivo microscopic retinal changes to visual function in patients who have various forms of retinal dystrophy. METHODS: The UC Davis Adaptive Optics (AO) fundus camera was used to acquire in vivo retinal images at the cellular level. Visual function tests consisting of visual fields, multifocal electroretinography (mfERG), and contrast sensitivity were measured in all subjects by using stimuli that were coincident with areas imaged. Five patients with different forms of retinal dystrophy and three control subjects were recruited. Cone densities were quantified for all retinal images. RESULTS: In all images of diseased retinas, there were extensive areas of dark space between groups of photoreceptors, where no cone photoreceptors were evident. These irregular features were not seen in healthy retinas, but were apparent in patients with retinal dystrophy. There were significant correlations between functional vision losses and the extent to which these irregularities, quantified by cone density, occurred in retinal images. CONCLUSIONS: AO fundus imaging is a reliable technique for assessing and quantifying the changes in the photoreceptor layer as disease progresses. Furthermore, this technique can be useful in cases where visual function tests provide borderline or ambiguous results, as it allows visualization of individual photoreceptors.     

Evaluation of retinal function using the Dynamic Focal Cone ERG

The development of effective means of assessing visual function in retinal disease holds the key to improved understanding of pathogenesis, and better monitoring of treatment outcomes. In diseases such as age-related macular degeneration, in which the primary locus of dysfunction is the outer retina, tests which provide a direct measure of the functional integrity of the photoreceptor/retinal pigment epithelium (RPE) complex are of great importance. Recovery of retinal function following adaptation to a bright light requires the healthy function of photoreceptors, RPE, Bruch's membrane and choroidal circulation, making an assessment of this recovery a potentially useful clinical tool. However, current techniques are either subjective in nature, or are influenced by post-retinal processing of visual information. This report describes a novel technique, the 'Dynamic Focal Cone Electro-retinogram (ERG)', which allows direct, objective assessment of the recovery of macular function following photopigment bleach. A series of 41 Hz ERGs was recorded, and ERG amplitude was plotted as a function of time following cessation of the bleach. Normative data was collected from 10 healthy subjects. For all subjects, there was no measurable ERG immediately after the bleach, but the amplitude had returned to a pre-bleach level within 4 min. The amplitude recovery data were adequately described both by an exponential recovery function and by a model based on a rate-limited recovery process. We conclude that this technique provides a clinically applicable, objective measure of outer retinal recovery.     

Detailed analysis of retinal function and morphology in a patient with autosomal recessive bestrophinopathy (ARB)

The objective of the paper is to study the retinal microstructure and function in a patient with autosomal recessive bestrophinopathy (ARB). Retinal function and morphology assessment in a patient diagnosed with a biallelic mutation in the BEST1 gene (heterozygote mutations: Leu88del17 and A195V) included: full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG), electro-oculogram (EOG) testing, and imaging with a high-resolution Fourier-domain optical coherence tomography (Fd-OCT) system (UC Davis Medical Center; axial resolution: 4.5 μm, acquisition speed: 9 frames/s, 1,000 A-scans/frame) combined with a flexible scanning head (Bioptigen Inc.). The 11-year old asymptomatic boy showed a well-demarcated retinopathy with deposits. Functional assessment revealed normal visual acuity, reduced central mfERG responses, delayed rod and rod-cone b-wave ffERG responses, and reduced light rise in the EOG. Fd-OCT demonstrated RPE deposits, photoreceptor detachment, elongated and thickened photoreceptor outer segments, but preserved inner retinal layers. In conclusion, ARB associated retinal dystrophy shows functional and morphological changes that overlap with classic Best disease. For the first time, high-resolution imaging provided in vivo evidence of RPE and photoreceptor involvement in ARB.     

Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration

Background To evaluate inner-retinal function by pupillary constrictions and phosphenes evoked by transcorneal electrical stimulation (TES) in patients with hereditary retinal degeneration.Methods Consecutive 20 eyes of 20 patients (16 with retinitis pigmentosa (RP); and four with cone-rod dystrophy (CRD)) whose visual acuity was equal to or worse than 20/2000 at Osaka University Hospital and eight eyes of eight healthy subjects were enrolled. TES was performed on with a contact lens stimulating electrode. The electrically evoked pupillary response (EEPR) was recorded by a pupillometer, and the phosphenes by the subjective responses. Three electrical current thresholds were determined: T1, threshold current for initial phosphene; T2, threshold for eliciting a phosphene extending into the central field; and P, threshold for a relative pupillary constriction ≥3%.The EEPR and phosphene thresholds were compared with the visual acuity or the visual field.Results All T1, T2 and P were significantly higher in patients than in normals (Mann-Whitney, P<0.001). Both T1 and T2 were not correlated with visual acuity but depended on the area and location of the residual visual field. T1 and T2 in RP eyes with a EEPR was significantly lower than that in RP eyes without an EEPR. During TES, all subjects and patients had no pain, and no complications except for a slight corneal superficial punctuate keratopathy.Conclusions The safety and the efficacy of TES to estimate the residual inner-retinal function in patients with retinal degeneration indicate that TES can be used as one of the most important test to select candidates for retinal prostheses.This study was supported by Health Science Research Grants from the Ministry of Health, Labor and Welfare, Japan and by a grant from the Ministry of Education, Culture, Science and Technology (no.16591752). T. Morimoto was supported by the JSPS Research Fellowship for Young Scientists.     

Evaluation of an ex vivo model implication for carrier-mediated retinal drug delivery

PURPOSE: The purpose of this study was to evaluate the implication of an ex vivo model for carrier-mediated retinal drug delivery using an Ussing chamber system. METHODS: Dutch Belted Pigmented rabbits weighing 2-2.5 kg were used in these studies. Excised posterior segment tissues (RPE-choroid-sclera and sclera), mounted on the Ussing chamber, were used as an ex vivo model. Transport studies were carried out across sclera and RPE-choroid-sclera (RCS) tissue preparations in the sclera to retina (S --> R) and retina to sclera (R --> S) directions for 3 hr at 37 degrees C. The model was validated by permeability studies with paracellular and transcellular markers ([(3)H]mannitol and [(14)C]diazepam, respectively), tissue viability studies (bioelectrical and biochemical assays), and tissue histology and electron microscopy studies. Functional presence of a carrier-mediated transport system for folic acid (folate receptor alpha) was investigated on the basolateral side of the rabbit retina. RESULTS: Results from bioelectrical, biochemical, and histological evaluation of tissue provide evidence that the RCS tissue preparation remains viable during the period of transport study. Permeability values of [(3)H]mannitol across sclera were 4.18 +/- 1.09 x 10(- 5) cm/s (R --> S) and 4.11 +/- 1.09 x 10(- 5) cm/s (S --> R) and across RCS were 1.77 +/- 0.31 x 10(- 5) cm/s (S --> R) and 1.60 +/- 0.19 x 10(- 5) cm/s (R --> S). Permeability values of [(14)C]diazepam across sclera were 2.37 +/- 0.38 x 10(- 5) cm/s (R --> S) and 2.70 +/- 0.70 x 10(- 5) cm/s (S --> R) and across RCS were 3.12 +/- 0.12 x 10(- 5) cm/s (R --> S) and 2.77 +/- 0.25 x 10(- 5)cm/s (S --> R). The rate of [(3)H]folic acid transport across RCS was found to be significantly higher in the S -->R direction (16.34 +/- 0.94 fmoles min(-1) cm(-2)) as compared with R --> S direction (9.38 +/- 1.44 fmoles min(-1) cm(-2)) and nearly 10-fold higher across sclera as compared with RCS in both directions. Transport of [(3)H]folic acid was found to be pH and temperature dependent and was inhibited by 44.5%, 35.1%, and 50.3% in the presence of unlabeled folic acid, 5-methyltetrahydrofolate (MTF), and Methotrexate (MTX). CONCLUSIONS: The RCS tissue preparation mounted on the Ussing chamber system, an ex vivo model, can be a useful tool for identification and characterization of carrier-mediated systems present on RPE (a major barrier for retinal drug delivery) and to study carrier-mediated retinal drug delivery via prodrug derivatization.