Threshold power levels for NPe6 photodynamic therapy

OBJECTIVE: To determine the threshold power levels for producing retinal and choroidal vascular occlusion using mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy; to evaluate its efficacy with longer intervals between photosensitizer injection and laser application; to determine the elapsed time between light application and appearance of angiographic changes. METHODS: Pigmented and nonpigmented rabbits were injected intravenously with 2 mg/kg of NPe6 before laser irradiation of the retina-choroid. Group 1 was treated at increasing power levels; fluorescein angiograms were obtained at each fluence. Group 2 animals were exposed to laser irradiation at 5 minutes, and 1 and 3 hours postinjection to determine (by fluorescein angiography 24 hours post-treatment) if increasing the interval affected outcome. Group 3 animals underwent fluorescein angiography at 30 minutes, 1 hour, 2 hours, and 24 hours posttreatment to document the time between laser application and subsequent vessel closure. RESULTS: Choroidal vessel occlusion was angiographically evident in all lesions at fluences of > or = 2.65 J/cm2 in pigmented rabbits and at > or = 0.88 J/cm2 in nonpigmented rabbits. Lesion diameter decreased as the time between injection and treatment increased. Vessel occlusion was documented at least 2 hours after treatment. CONCLUSION: Choroidal vessel occlusion can occur at very low fluence.     

Experimental photodynamic effects of hypocrellin A on the choriocapillaris

OBJECTIVE: To investigate the use of the photosensitizer hypocrellin A as a photodynamic agent to occlude the choriocapillaris in the eyes of pigmented rabbits. METHODS: Hypocrellin A (500 microg/kg) incorporated into liposomes was injected intravenously in pigmented rabbits. Ten to 15 minutes later, the retinas were irradiated with a dye laser (spot size, 2 mm; 10-60 mW; 10-60 seconds; fluences 3.2 to 95.5 J/cm2) at two wavelengths: yellow (568 nm) and red (647 nm). Fluorescein angiography was performed 2 and 24 hours later. Parallel controls were irradiated without a photosensitizer. Histology was performed immediately after the 24-hour angiogram. observed 24 hours after PDT in eyes subjected to yellow laser irradiation at 20 mW for 60 seconds (fluence, 38.2 J/cm2) and at higher powers for lesser durations: 30 mW for 40 seconds (fluence, 38.2 J/cm2), 40 mW for 20 seconds (fluence, 25.4 J/cm2), and 50 and 60 mW for 10 seconds (fluences, 15.9 and 19.1 J/cm2, respectively). Light microscopy showed occlusion of the choriocapillaris in all eyes with angiographic responses. Control eyes and eyes irradiated with the red laser revealed no angiographic or histologic changes. CONCLUSION: Photodynamic therapy using liposomal hypocrellin A and the yellow laser of 568 nm was effective in occluding the choriocapillaris of pigmented rabbits.     

The effect of therapeutic soft contact lenses on antibiotic delivery to the cornea

The effects of high (71%) and low (38.6%) water content lenses on antibiotic delivery to the cornea were studied in rabbits by measuring corneal tobramycin concentrations 1, 2, 4 and 6 hours after topical application at intervals of 15 minutes. In the presence of the low water content lens corneal drug levels were higher than in control corneas for every time point assayed. This difference was only significant at 4 hours (P less than 0.05). In eyes wearing the high water content contact lens corneal drug concentration was also higher at every time point tested except one hour. The difference was significant only at 4 hours (P less than 0.01). The data suggest that in the normal, noninflammed eye, the presence of a therapeutic soft contact lens will not compromise aminoglycoside delivery to the cornea.     

Liposome-encapsulated3H-5FU in rabbits

We compared the pharmacokinetics of liposome-encapsulated tritiated 5-fluorouracil (³H-5FU-Lipo) to³H-5FU in buffered saline (³H-5FU-PBS) after subconjunctival or intravitreal injection into rabbit eyes. Liposomes were prepared using phosphatidylcholine, phosphatidic acid, and alpha-tocopherol. Following a unilateral subconjunctival injection of either³H-5FU-Lipo or³H-5FU-PBS, rabbits were sacrificed at 0.5, 1, 4, and 8 hours. Significantly higher (p<0.05) drug levels were achieved with the encapsulated drug in the vitreous at all four time points and in the aqueous at three of four time points.Following bilateral intravitreal injections of 500 µg of 5FU in 0.1 ml, as either³H-5FU-Lipo or³H-5FU-PBS injected rabbits were sacrificed at 0, 6, 12, 24, and 48 hours. Vitreal drug levels were significantly higher (p<0.05) with encapsulated drug at all time points from 6 hours on. At 48 hours, the vitreal level with the encapsulated drug was 578±0.23 µg/ml compared with 1.06±0.07 µg/ml for³H-5FU-PBS.     

Uptake and clearance of 5-fluorouridine following subconjunctival and intravitreal injection

Described are some pharmacokinetic parameters for 5-fluorouridine, a potentially useful intermediate metabolite of 5-fluorouracil (5-FU), following subconjunctival and intravitreal injection in the pigmented rabbit. Immediately following a 500 microgram intravitreal injection of 3H-5-fluorouridine, a peak ipsilateral vitreous concentration of 308 micrograms/ml was measured. This decreased to 199 micrograms/ml at 2 hours, 33 micrograms/ml at 12 hours and 4.4 micrograms/ml at 24 hours, indicating that 5-fluorouridine is cleared from the vitreous at a rate similar to 5-fluorouracil. Aqueous concentrations in the ipsilateral eye reached a maximum at 6 hours (9.6 micrograms/ml) and decreased to 0.8 micrograms/ml at 24 hours. Following subconjunctival injection of 5 mg 3H-5-fluorouridine (0.5 ml), peak ipsilateral anterior chamber concentration of 10.7 micrograms/ml was measured 1 hour after injection and decreased to 2.4 micrograms/ml after 12 hours. Maximum vitreal concentrations of 1.7 micrograms/ml were measured 12 hours after injection.     

Transpupillary thermotherapy threshold parameters: effect of indocyanine green pretreatment

PURPOSE: To evaluate the effect of combined treatment with systemic indocyanine green (ICG) on threshold fluence levels of transpupillary thermotherapy (TTT) in rabbits. METHODS: Four pigmented rabbits and 13 nonpigmented rabbits were studied. TTT was performed on normal rabbit choriocapillaris using an 810-nm diode laser via slit-lamp biomicroscope delivery through a Goldmann macular lens. Laser spot size, power, and duration of laser exposure were varied to achieve a range of TTT fluences for threshold testing in both albino and pigmented rabbit fundi. Intravenous ICG pretreatment at doses of 0.41 to 10 mg/kg was initiated at varying times before TTT treatment. After the experiment, the eyes were enucleated under deep anesthesia, the animals were killed, and the eyes were prepared for light microscopy. RESULTS: When intravenous ICG pretreatment was employed, there was a dose-dependent decrease in the TTT fluence threshold as compared with known threshold values. At threshold fluences, histopathologic sections revealed damage to all layers of the retina in addition to choriocapillaris damage. CONCLUSION: Intravenous ICG pretreatment can be used to lower the TTT threshold fluence and irradiance required to create angiographically visible lesions in the normal rabbit choriocapillaris. Damage was seen in all layers of the retina and choriocapillaris at threshold levels when TTT was used alone or in combination with ICG pretreatment.     

Ocular pigmentation and intraocular pressure response to forskolin

We studied the effects of a forskolin suspension on intraocular pressure (IOP) in normal albino and pigmented rabbits and in alpha-chymotrypsin induced ocular hypertensive rabbits. Experimental-induced ocular hypertensive rabbits were produced by injecting of alpha-chymotrypsin (167 units) into the posterior chamber of the eye of albino rabbits. Ocular hypertensive rabbits were classified into 3 groups according to the IOP (Group A; 15-19 mmHg, B; 20-24 mmHg, C; 25-29 mmHg). Topical application of 1% forskolin caused a significant decrease in IOP in Groups B and C, as well as in normal albino and pigmented rabbits. The hypotensive effects were lower in pigmented rabbits than in albino rabbits, although the duration was longer. Subconjunctival injection of 1% forskolin reduced IOP 1 to 5 hrs after treatment in albino rabbits. However, in pigmented rabbits, a slight increase in IOP was observed at 30 min, followed by a significant decrease 5 to 10 hrs after injection. Furthermore, the binding ability of forskolin to melanin granules was determined in vitro. Forskolin exhibited specific affinity towards melanin granules obtained from bovine eyes, with the binding reaching a plateau after 5 min of incubation.     

比较5-Fu和MMC缓释膜在青光眼滤过手术中应用的实验研究

目的 评估生物缓释膜在青光眼滤过手术中的安全性和作用,比较5-氟尿嘧啶(5-Fu)和丝裂霉素(MMC)缓释膜在青光眼滤过手术中的抗增殖的疗效.方法 以5-Fu和MMC作为模型药物,壳聚糖作为载体,溶剂挥发法成膜;通过共价交联的方式将12μg的5-Fu或MMC结合到生物缓释膜上.未植入缓释膜作为对照组,其余3组植入空白、5-Fu和MMC缓释膜.四组均行青光眼滤过手术,静脉留置针作为引流管,空白缓释膜、5-Fu缓释膜、MMC缓释膜缝于巩膜瓣下.滤过手术前和手术后1、3、5、714、21和28d,以Tonopen眼压计记录兔眼压,以裂隙灯观察滤过泡大小和眼前节的变化并照相;分别于术后28d每组处死两只兔,总共8只眼标本行病理组织学检查;用扫描电子显微镜检测每组术后28d的角膜和晶状体标本.结果 术前各组平均眼压无差异,MMC组手术前和手术后28d内比较差异有统计学意义(F值为26.866 P＜0.01),5-Fu组和单纯引流管组手术前和手术后14d内比较差异有统计学意义,(F值分别为13.467,6.567 P＜0.01),空白缓释膜组手术前和手术后7d内比较差异有统计学意义(F值分别为11.426 P＜0.01);MMC、5-Fu组滤过泡生存时间优于单纯引流管组、空白缓释膜组.5-Fu和MMC组,术后28d角膜内皮细胞和晶状体前囊无异常改变.结论 5-Fu和MMC生物缓释膜能明显提高滤过手术成功率并且是安全的,在降低眼内压和延长滤过泡减少眼前节并发症方面,MMC缓释膜比5-Fu缓释膜能更有效地提高滤过手术成功率.     

Mechanism of photodynamic occlusion using liposomal Zn(II)-phtalocyanine

PURPOSE: To evaluate the potential of liposomal Zinc(II)-phthalocyanine (ZnPc) to selectively target subretinal vasculature. METHODS: Photodynamic therapy (PDT) with liposomal Zinc(II)-phtalocyanine was used to induce choroidal occlusion in eyes of pigmented rabbits. Drug doses of 0.16, 0.24, 0.32, and 0.4 mg/kg body weight were administered. Photosensitization was performed at a wavelength of 671 nm and an irradiance of 100 mW/cm2 applying fluences of 5, 10, 20, and 50 J/cm2. RESULTS: Using liposomal ZnPc, occlusion of choroidal vessels was achieved without damage to the overlying neurosensory retina. A tight dose correlation was found with a drug dose of 0.32 mg/kg and a light dose of 10 J/cm2 inducing a selective thrombosis of the subretinal capillary layer. Histology revealed a selective intravascular alteration of the endothelial cells. CONCLUSIONS: PDT using liposomal ZnPc allows occlusion of subretinal vasculature with maintenance of neuroretina and RPE. The destructive effect on choroidal vascular endothelium is intensive.     

Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits

The ocular toxicity of liposome-intercalated amphotericin B and commercial amphotericin B were compared after intravitreal injection in healthy pigmented rabbits. Ophthalmoscopic observations over 5 weeks following a single intravitreal injection showed vitreal band formation and focal retinal damage after doses of commercial amphotericin B as low as 5 micrograms. Such lesions were not seen in animals given liposomal amphotericin B in doses up to 20 micrograms. Histopathologic examination showed areas of retinal atrophy or necrosis in five of 16 rabbits given commercial amphotericin B in doses of 5-20 micrograms but in none of 16 rabbits given the same doses of liposomal amphotericin B (P = 0.02). Small white vitreal bodies were seen clinically in virtually all animals given liposomal amphotericin B or "empty" (drug-free) liposomes but in only a few animals given commercial amphotericin B; these deposits may represent residual lipid. Concentrations of amphotericin B ranged from 0.4 to 1.0 micrograms per ml of vitreous humor 5 weeks after injection of 5-20 micrograms of either formulation. These studies indicate that liposome association markedly reduces the ocular toxicity of amphotericin B.     

Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits

Purpose: This study aimed to develop low‐viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits. Methods: Aqueous eyedrops with hydroxypropyl‐β‐cyclodextrin containing 0.01–2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments ± standard error of the mean) are expressed as the change from baseline (24.7 ± 3.3 mmHg). Results: Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf‐life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 ± 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 ± 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10–22 hours after administration and duration of up to 32 hours. Conclusions: Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low‐viscosity aqueous eyedrop formulations.     

褪黑素对高糖诱导白内障形成抑制作用的实验研究

目的:观察褪黑素(melatonin,MLT)对高糖诱导体外培养兔晶状体白内障形成的抑制作用。方法:选取发育正常的兔晶状体,随机分为3组:A组空白对照组、B组高糖处理组、C组实验组(在高糖处理的基础上加MLT,浓度为50μmol/L)。观察不同培养时间(48,72,96h)各组晶状体混浊程度。通过黄嘌呤氧化酶法测定超氧化物歧化酶(superoxide dismutase,SOD);化学比色法测定过氧化氢酶(catalase,CAT);硫代巴比妥酸法测定丙二醛(malondialdehyde,MDA),观察不同时间各组晶状体的生物化学变化。结果:晶状体混浊情况:培养96h后,A组晶状体无明显变化,晶状体完全透明为80%,Ⅱ级混浊为20%;B组晶状体混浊逐渐加重,晶状体Ⅳ级混浊为20%,Ⅴ级混浊为80%;C组晶状体完全透明为60%,Ⅱ级混浊为40%。晶状体生化指标的测定:C组兔晶状体组织中的SOD,CAT含量高于B组(P<0.01),C组兔晶状体组织中MDA含量低于B组(P<0.01)。结论:MLT可抑制高糖诱发的兔晶状体的氧化损伤,延缓和减轻高糖诱导的兔白内障的发生和发展。     

Posterior segment ocular pharmacokinetics using microdialysis in a conscious rabbit model

PURPOSE: To develop and establish a conscious rabbit model for ocular pharmacokinetic studies and to delineate the effects of anesthesia and probe implantation on the ocular disposition of ganciclovir. METHODS: A conscious rabbit model was developed for microdialysis of the posterior ocular segment. Rabbits were divided into three groups. Group I consisted of rabbits with no recovery period after probe implantation and were anesthetized throughout the experiment. Group II consisted of rabbits that had a more than 5-day recovery period and were conscious during the experiment. Group III consisted of rabbits that had a more than 5-day recovery period and were anesthetized during the experiment. (3)[H] ganciclovir was administered (50 microL) intravitreously in all groups, and ocular levels were determined for 10 hours at appropriate time intervals. Data obtained were subjected to noncompartmental modeling. RESULTS:Probe calibration studies indicated that the probes were functional for at least 14 days. The anesthetized groups, regardless of the period of recovery from probe implantation, exhibited higher areas under the curve than did the conscious group. The vitreous half-life of ganciclovir was significantly shorter in the groups with a recovery period of more than 5 days compared with the group with no recovery period. CONCLUSIONS: The conscious rabbit model was developed and can be used for a period of at least 14 days. Anesthesia increased ocular bioavailability of intravitreously administered ganciclovir, whereas probe implantation led to increased protein efflux into the vitreous, which may be the reason for the increased half-life of ganciclovir in group I.     

Ocular pharmacokinetics of fluocinolone acetonide after Retisert intravitreal implantation in rabbits over a 1-year period.

PURPOSE: The present study was designed to examine the pharmacokinetics of a fluocinolone acetonide (FA) intravitreal implant in pigmented rabbits. METHODS: Pigmented rabbits were randomly assigned to receive either a 0.5 mg or 2.0 mg FA intravitreal implant (Retisert). Four animals were sacrificed per time point (2 hours; 2 weeks; and 3, 6, 9, and 12 months after implantation) for FA intraocular levels determination. RESULTS: In the vitreous, concentration of FA was relatively constant from the first time point, 2 hours, through 1 year, and dose-related, approximately seven- to eight-fold greater in the 2-mg implant. Concentrations of FA were generally higher in the vitreous (11-18 and 75-146 ng/g) and retina (42-87 and 224-489 ng/g) than in the aqueous humor (0.21-1.1 and 2.6-13.0 ng/g) for the 0.5- and 2-mg implants, respectively. Urine and plasma values were below the lower limit of quantitation (200 pg/mL) for all observations, indicating no evidence of systemic absorption. CONCLUSIONS: In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility.     

Collagen shield delivery of amphotericin B

By using a high-pressure liquid chromatography assay, we investigated the ability of collagen shield therapeutic contact lenses to release amphotericin B and deliver it to the anterior segment of rabbit eyes. In vitro studies showed that presoaked collagen shields released most of the amphotericin B within the first hour of elution. We compared the corneal and aqueous humor amphotericin B levels produced by collagen shields soaked in amphotericin B and frequent-drop therapy at four time points over a six-hour period. The collagen shields soaked in amphotericin B produced corneal levels that were higher than those produced by frequent-drop therapy at one hour, equivalent to drop therapy at two and three hours, and lower than drop therapy at six hours. There were no differences in amphotericin B levels in aqueous humor at any time point between rabbits treated with collagen shield delivery and rabbits treated with frequent-drop delivery. The results of this study suggest that amphotericin B delivery to the cornea by collagen shields is comparable to frequent-drop delivery but has the potential benefit of added convenience and compliance.     

Further evaluation of collagen shields as a delivery system for 5-fluorouracil: histopathological observations

Collagen shields are a potential delivery system for antifibroblast drugs such as 5-fluorouracil after filtration surgery. To determine whether collagen shields produce histologic evidence of inflammation when implanted subconjunctivally, shields were implanted into four rabbit eyes and six guinea pig eyes and retained for 7 or 14 days. Two rabbit eyes and two guinea pig eyes served as controls. Seven days after implantation in the rabbit eyes foreign-body giant cells were present at the surface of the shield, and early deposition of connective tissue was evident around the shield. The inflammatory response at 14 days was similar but more intense. In the guinea pig eyes the collagen shields induced substantially less inflammation, and there was marked shield degradation at 14 days. The results suggest that the inflammatory response in rabbits may be species specific and that collagen shields may be of value as a drug-delivery system for antifibroblast drugs in other species.     

Comparative distribution of pilocarpine in ocular tissues of the rabbit during administration by eyedrop or by membrane-controlled delivery systems.

We compared the patterns of pilocarpine distribution in the rabbit eye during two regimens that were comparably efficacious in human clinical use: an administration of 2% pilocarpine nitrate eyedrops, every six hours, for four and eight days, and a continuous delivery of pilocarpine for as long as eight days, at 20 mug/hr, from a membrane-controlled delivery system in the inferior cul-de-sac. Pilocarpine labeled with radioactive carbon (14C) was used as a tracer. With administration of eyedrops, 14C levels in ocular tissues rose and fell within each six-hour interval between eyedrops, but with the delivery system, 14C levels remained constant over the two- to eight-day period. In each tissue, the 14C level within the first hour after the most recently administered eyedrop always exceeded the constant level maintained by the delivery system. Three to six hours after eyedrop administration, the 14C levels in cornea, iris, and sclera were approximately equal to those maintained by the delivery system. However, in lens, vitreous humor, and conjunctiva, the 14C levels were always two to five times higher with eyedrop administration than with the delivery system. Only aqueous humor showed a significantly lower 14C level with eyedrops than with the delivery system, occurring late in the interval between eyedrops. Compared to eyedrop administration, the membrane-controlled delivery system produced drug levels in ocular tissues that were constant rather than variable with time, and appreciably lower in tissues where the drug made no known contribution to the reduction of pressure.     

万古霉素在正常兔眼和细菌性眼内炎兔眼内的药代动力学研究

背景万古霉素近年来常被作为金黄色葡萄球菌性眼内炎治疗的首选药物,万古霉素在眼内药代动力学的研究报道较少。目的观察万古霉素在正常兔眼和细菌性眼内炎兔眼房水、玻璃体及血清中质量浓度的变化,并进行药代动力学参数比较。方法选取健康成年兔72只,采用随机数字表法分为正常组和眼内炎组,每组36只。眼内炎组兔右眼玻璃体腔内接种2000CFU／ml金黄色葡萄球菌建立眼内炎模型,注射后72h待出现典型的眼内炎表现时,兔眼玻璃体腔内注射10g／L万古霉素注射液0．1ml,分别于注射后0．5、2、4、6、12、24、48、72、84h经兔耳缘静脉采血2ml,之后以空气栓塞法处死动物,摘除眼球,收集房水和玻璃体,利用高效液相色谱仪紫外（HPLC—UV）法检测万古霉素在血液、房水和玻璃体内的质量浓度。3p97药代动力学软件拟合药代动力学参数。结果HPLC法的准确度和精确度符合生物样品的检测要求。玻璃体腔内注射万古霉素后,其在正常兔眼内的代谢呈二室模型,拟合曲线的高峰质量浓度Cmax分别为50．16mg／L和751．42mg／L,t1/2为51．04h和53．21h;其在金黄色葡萄球菌性眼内炎兔眼中代谢呈一室模型,高峰质量浓度Cmax分别为24．94mg／L和687．66mg／L,t1/2分别为11．42h和12．91h,2组动物血药质量浓度均较低,差异无统计学意义（P〉0．05）。正常组和眼内炎组玻璃体腔内注射万古霉素后随时间延长,玻璃体中万古霉素的质量浓度逐渐下降,而房水中出现先升高后下降的趋势。与正常组相应时间点比较,眼内炎组玻璃体和房水中万古霉素的质量浓度均明显下降,差异均有统计学意义（P〈0．05,P〈0．01）。结论HPLC能满足万古霉素药代动力学分析的需要;万古霉素在正常兔眼内的质量浓度较高,清除缓慢,而在细菌性眼内炎兔眼中质量浓度较低、清除较快。     

Fluctuations in intra-ocular pressure with sleep:

Intra-ocular pressure (IOP) was measured immediately after normal subjects were woken from at least 5 hours sleep. Measurements were made at approximately 15 s intervals, for about 20 minutes. The IOP of all 14 subjects was elevated after sleep and returned to baseline levels with a time course which was approximately exponential; the longest time constant of return of IOP to baseline was 1056.9 s, and the shortest 133.5 s. Mean time constant of recovery was 404.8 s. The decrease in IOP may be related to melatonin levels which increase during sleep and decrease in the light, or be related to accommodation and eye movements which may act to 'pump' aqueous from the eye.     

外伤性眼内炎兔房水中细胞因子的表达

目的分析干扰素(interferon-γ,IFN-γ)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-8(interleukin-8,IL-8)、转化生长因子-β(transforming growth factor-β,TGF-β)在兔眼外伤后不同时间房水中的浓度变化,探讨眼内炎的发病机制。方法将18只实验兔随机分为3组,每组6只兔。Ⅰ组为正常对照组,Ⅱ组和Ⅲ组右眼建立外伤性眼内炎模型,并将金黄色葡萄球菌接种于Ⅲ组受伤眼的玻璃体内。ELISA法测定造模前及造模后6h、12h、24h、48h、96h房水中IFN-γ、IL-6、IL-8、TGF-β的浓度;于6h、12h、24h、48h、96h、8d、16d分别用裂隙灯及间接显微镜观察眼部炎症情况并评分。结果造模后Ⅱ组炎症反应明显较Ⅲ组轻,造模12h后两组各时间点临床炎症评分间差异均有统计学意义(均为P<0.05)。Ⅱ组和Ⅲ组兔房水中IFN-γ在造模后均升高,24h时达到高峰,分别为(516.45±20.80)ng.L-1、(508.21±31.45)ng.L-1,与造模前(337.15±17.25)ng.L-1相比差异均有统计学意义(均为P<0.05);造模后24hIL-6在Ⅱ组和Ⅲ组兔房水中的浓度即达到高峰,分别为(61.69±2.11)ng.L-1、(61.81±2.18)ng.L-1,与造模前(46.34±2.09)ng.L-1相比差异均有统计学意义(均为P<0.05);Ⅱ组和Ⅲ组兔房水中IL-8在造模后48h浓度达到高峰,分别为(66.78±2.00)ng.L-1、(64.94±3.39)ng.L-1,与造模前(44.50±1.40)ng.L-1相比差异均有统计学意义(均为P<0.05)。造模后24hTGF-β在Ⅱ组和Ⅲ组兔房水中的浓度最低,分别为(288.79±7.17)ng.L-1、(293.99±1.93)ng.L-1,与造模前(404.45±2.86)ng.L-1相比差异均有统计学意义(均为P<0.05)。结论外伤性眼内炎导致机体免疫系统破坏,房水中细胞因子表达发生变化,因此在眼内炎的早期,应联合采取免疫干预措施来控制炎症反应。