title: Feasibility study of chitosan as intravitreous tamponade material.
abstract: BACKGROUND
  Chitosan can inhibit fibroblastic proliferation by suppressing fibroblast cells, and has the similar physiological characteristics as normal vitreous body, so it might have the potential to become vitreous filling material and might possibly inhibit proliferative vitreous retinopathy. To investigate the possibility of chitosan as vitreous filling material, this study was designed to investigate retina, ciliary body, lens and cornea morphology changes, intraocular pressure and intraocular inflammatory factors fluctuating after chitosan intravitreous tamponade.
  
  
  METHODS
  Fifteen healthy chinchilla rabbits were chosen; three of them were a blank (negative) control group without any surgical procedure. The remaining 12 rabbits received vitrectomy on both eyes; all the right eyes (experimental group) were given 1.2-1.8 ml (average 1.5 ml) of chitosan intravitreously, while sodium hyaluronate were given in the left eyes (control group). All eyes underwent slit-lamp biomicroscope and indirect ophthalmoscope examination and intraocular pressure measurement pre- and post-op. The concentration of IL-6, IL-8 (radioimmunoassay), NO (nitrate reductase method) in aqueous humor and vitreous body were tested at day 15 and day 30 post-op. At day 30 post-op, the cornea, ciliary body, and lens were dissected for light microscopy examination, and the retinal tissues 2PD away from the optic disc on the vertical orientation of posterior pole were dissected for light- and electro-microscope examination.
  
  
  RESULTS
  The conjunctival congestion and slight inflammatory response in the anterior chamber disappeared within 7 days post-op. During the 30-day experiment, cornea, lens and the filling material in vitreous cavity were transparent in all animals. The retina was attached without proliferation. The intraocular pressure in the experimental group post-op fluctuated between 4.55 +/- 2.94 and 6.25 +/- 2.37 mmHg, which was not significantly different from the situation pre-op (6.18 +/- 1.19 mmHg) (P > 0.05). The intraocular pressure in the control group post-op fluctuated between 5.10 +/- 2.51 and 5.90 +/- 2.49 mmHg, which was not significantly different from the situation pre-op (6.50 +/- 0.94 mmHg) (P > 0.05). There was also no significant difference in the intraocular pressure post-op at different time points between the experimental group and control group (all P > 0.05). At day 15 post-op, IL-6 concentration in aqueous humor were 37.31 +/- 8.59 ng/ml and 39.52 +/- 9.69 ng/ml in experimental group and control group respectively, both higher than those in the blank control group (26.55 +/- 9.34 ng/ml) (P < 0.05). IL-8 concentration were 7.00 +/- 3.79 ng/ml and 6.32 +/- 3.68 ng/ml respectively, no significant difference to the blank control group (4.72 +/- 1.71 ng/ml) (P > 0.05): the concentrations of NO were 63.94 +/- 26.80 micromol/ml and 51.81 +/- 13.19 micromol/ml respectively, no significant difference to the blank control group (50.36 +/- 15.67 micromol/ml) (P > 0.05). At day 30 post-op, the concentrations of IL-6, IL-8 and NO in aqueous humor showed no significant difference among all three groups (P > 0.05). In vitreous body at day 30 post-op, the concentrations of IL-8 in experimental group and control group were 10.17 +/- 3.63 ng/ml and 10.69 +/- 3.52 ng/ml, and those of NO were 50.23 +/- 19.69 micromol/mL and 50.60 +/- 12.72 micromol/mL respectively, all higher than in the blank control group (30.37 +/- 14.63 micromol/ml) (P < 0.05); the concentrations of IL-6 were 24.51 +/- 10.71 ng/ml and 26.36 +/- 13.00 ng/ml, no significant difference to the blank control group (24.06 +/- 5.98 ng/ml) (P > 0.05). At various time points, there was no significant difference in the concentrations of IL-6, IL-8 and NO in aqueous humor and vitreous body in the experimental group and the control group (P > 0.05). There was no morphological change found under light microscopy in cornea, ciliary body and lens. The outer plexiform layer of retina was thinner, but no significant degeneration, necrosis, karyopyknosis or lysis were found under the ultrastructural microscopy.
  
  
  CONCLUSIONS
  Chitosan intravitreous tamponade has no significant effect on the histology of the eye, doesn't cause intraocular pressure to fluctuate, and slightly increases inflammatory factors (IL-6, IL-8, NO) in comparison to the normal levels, but with no significant difference from the effects caused by sodium hyaluronate, which indicated chitosan might not lead to a clinically significant inflammatory response. It suggests that chitosan could be used as intravitreous tamponade material.
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. hyang@tjh.tjmu.edu.cn
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Gu
authors.forename: Xiaonong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects* / Q000473:pathology; D001082:Aqueous Humor / Q000378:metabolism; D001672:Biocompatible Materials / Q000633:toxicity*; D048271:Chitosan / Q000633:toxicity*; D002924:Ciliary Body / Q000187:drug effects / Q000473:pathology; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D005240:Feasibility Studies; D006490:Hemostatics / Q000633:toxicity*; D007267:Injections; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects*; D007908:Lens, Crystalline / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000648:ultrastructure; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D006490:Hemostatics; D015850:Interleukin-6; D016209:Interleukin-8; D009569:Nitric Oxide; D048271:Chitosan