Experimental study of cellular response on the intraocular lens surface in terms of the presence and distribution of fibronectin

An immunohistochemical study was performed to observe cellular proliferation on the surface of implanted intraocular lenses (IOLs) in rabbit eyes. Rabbits were killed 3-28 days postoperatively. The removed IOLs were examined by an immunoperoxidase staining method using anti-fibronectin antibodies. The immunoreactivity for fibronectin was detected in macrophages and multinucleated giant cells attached to the IOL surface. Prominent stains were observed in these cells 1 week after the operation, and staining for fibronectin was less intense in the specimens 2 and 4 weeks after implantation. Fibronectin is produced by macrophages and multinucleated giant cells on the IOL surface, and might play important role in cellular adhesion and motility. Fibronectin immunoreactivity decreased with time and it may be related to cellular activity.     

Cellular adhesiveness on implanted lenses in monkeys

Cells are known to adhere to implanted intraocular lenses (IOLs), but the mechanisms of this adhesiveness are not known. We studied cellular adhesiveness on four posterior chamber IOLs that had been implanted into monkey eyes. The animals were killed at 4 and at 7 days after lens implantation. The IOLs were removed and examined by transmission electron microscopy. At 4 days after IOL implantation, macrophages were attached to the IOL surface; at 7 days after implantation, multinucleated giant cells were attached to the IOL surface. These cells had bundles of microfilaments in the subplasmalemmal region of areas of close cell-IOL apposition. These microfilaments may play an important role in the cellular adhesiveness on the surface of implanted IOLs.     

Evaluation of cellular adhesions on silicone and poly(methyl methacrylate) intraocular lenses in monkey eyes: An electron microscopic study

PURPOSE: To assess the biocompatibility of intraocular lens (IOL) material by studying the number of cells adhering to IOLs in monkey eyes. SETTING: Department of Ophthalmology, Kyushu University, Fukuoka, Japan. METHODS: Silicone or poly(methyl methacrylate) (PMMA) IOL implantation was performed in 21 monkeys. One eye of each animal had surgery. The IOL-implanted eyes were enucleated 1, 2, 3, 5, and 7 days and 1, 3, 4, 5, and 9 months after the procedure. One eye was studied at each time. Cells on the anterior IOL surface were photographed using a scanning electron microscope, counted and assessed with NEC, Graphtec, and Nikon equipment, and then observed using a transmission electron microscope. RESULTS: Leukocytes, macrophages, and giant cells were found on the anterior IOL surface. Numerous cells were observed on the PMMA IOLs in the early postoperative period; they gradually decreased. Few cells were seen on the silicone IOLs during the course of the study. The giant cells became larger during the postoperative period. CONCLUSION: The foreign-body reaction to silicone IOLs in monkey eyes was less than that to PMMA IOLs.     

Cellular reaction on the anterior surface of 4 types of intraocular lenses

PURPOSE: To assess the cellular reaction on the anterior surface of 4 types of foldable intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University Hospital of Vienna, Vienna, Austria. METHODS: One hundred eyes scheduled for cataract surgery were prospectively randomized into 4 groups of 25 eyes each using random number tables. Group 1 received a Hydroview IOL (Bausch & Lomb), Group 2 an AcrySof IOL (Alcon), Group 3 a MemoryLens IOL (ORC), and Group 4 a CeeOn 920 IOL (Pharmacia). Patients were examined 1, 3, 7, 30, 90, and 180 days postoperatively. Postoperative biomicroscopic examinations were done with a slitlamp, and a specular microscope was used to document the presence of cell deposits and identify areas with the highest density of cells. RESULTS: The local tissue response revealed 2 patterns: a nonspecific foreign-body reaction to the IOL (small round, fibroblast-like, epithelioid, and giant cells) and a lens epithelial cell (LEC) reaction. The highest incidence of LECs was in the Hydroview group, in which LECs were present on 81.8% of lenses 180 days postoperatively. During the first postoperative days, small round and fibroblast-like cells were found on all IOLs. From 7 days on, the incidence and density of these cells were less severe in the Hydroview and CeeOn 920 groups. After several weeks, epithelioid cells and foreign-body giant cells were seen on some IOLs. These cells appeared more often on AcrySof, MemoryLens, and CeeOn IOLs. CONCLUSION: This study found IOL-related differences in cellular reaction after cataract surgery. The incidence of a nonspecific foreign-body reaction to 4 IOLs is consistent with the results of previous studies. The incidence of LECs was highest in the Hydroview group and lowest in the AcrySof group. The CeeOn 920 group had the lowest incidence of all types of cells.     

Phagocytosis and fibronectin of cells observed on intraocular lenses.

The phagocytic activity and distribution of fibronectin in the cells adhering to implanted intraocular lenses (IOLs) were studied in rabbits. IOLs were explanted from the posterior chamber 7 days after implantation. Phagocytosis by the cells from the IOLs was studied by electron microscopy after incubation with polystyrene beads. The distribution of fibronectin was examined immunohistochemically using an anti-fibronectin antibody. Many presumed macrophages and giant cells which were thought to be of macrophagic origin were observed on the IOLs. Adherence of the beads to the surface of the cells, phagocytosis of these beads, and fibronectin immunoreactivity were prominent in these presumed macrophages, whereas giant cells displayed a reduction in these activities. These findings suggest that the adherence activities of the presumed macrophages are less after giant cells are formed, reflecting a reduced production of fibronectin.     

Cellular fibronectin on intraocular lenses explanted from patients

We investigated the origin of fibronectin (FN) on five posterior and four anterior chamber explanted intraocular lenses (IOLs) using immunohistochemical methods. Cellular deposits (assumed to be macrophages) and fibrous or membrane-like proteinaceous deposits on the IOLs showed immunoreactivity to an antibody against cellular FN. These proteinaceous deposits were believed to be products of the cells that adhered to the IOLs.     

氟-肝素修饰的人工晶状体表面黏附细胞的实验研究

目的 观察猕猴眼内氟－肝素表面修饰的人工晶状体（intraocular lens,IOL)表面细胞的反应情况,研究修饰后IOL的生物相容性。方法 健康猕猴10只（20只眼）分为修饰和未修饰两组,分别植入氟－肝素表面修饰和未修饰的IOL。于术后180d和360d对取出的IOL进行光镜、扫描电镜及计算机图像分析。结果 IOL光学中心表面黏附细胞较少,周边部黏附细胞较多。细胞黏附面积最大者为巨细胞,数量最多者为巨噬细胞。修饰组IOL表面黏附细胞少于未修饰组;修饰的IOL表面附着细颗粒样的蛋白膜,未修饰的IOL表面附着纤维网状及颗粒样的蛋白膜。结论 氟－肝素表面修饰的IOL生物相容性优于未修饰的IOL。     

Is chronic intraocular inflammation after lens implantation of bacterial origin?

In an effort to better understand the cause of chronic intraocular inflammation after intraocular lens (IOL) implantation, both scanning and transmission electron microscopy were used to compare 1 anterior chamber, 1 iris-fixated, and 3 posterior chamber IOLs removed for this condition between 2 and 16 months after implantation with 8 IOLs explanted for other reasons (decentration in 4 cases, bullous keratopathy in 4 cases). Colonization with non-slime-producing, as well as slime-producing bacteria (1 case) in the presence of a thin membranous structure of cellular origin (multinucleated giant cells and macrophage-like cells) was demonstrated on all of the 5 IOLs explanted from inflamed eyes. Neither bacteria nor membranous structures could be identified on the IOLs removed because of dislocation or from eyes with bullous keratopathy. These observations indicate that bacterial colonization and the consequent host response may be characteristic features of many otherwise unexplained cases of intraocular inflammation after IOL implantation.     

Effects of surface modification of intraocular lenses on foreign body reaction

PURPOSE: In order to improve biocompatibility, we investigated the effects of surface modification by 2-methacryloyloxyethyl phosphorylcholine (MPC) on the foreign body reaction of intraocular lens (IOLs). MATERIALS AND METHODS: Materials of the IOLs were polymethylmethacrylate, hydrophobic acryl, and MPC surface-modified hydrophobic IOLs (MPC modified acryl). In an in vitro study, cultured macrophages sampled from mouse intra-abdominal exudate were cultured on a plate for each IOL material. The cell density and morphology of attached cells on the IOL materials were investigated. In an in vivo study, each IOL material was implanted in the peritoneal space of mice and foreign body reaction was investigated with a light microscope and a scanning electron microscope. RESULTS: In the in vitro study, the cells on the MPC modified acryl IOL material were remarkably fewer than those on the plates of the other two IOL materials. Regarding the implanted IOL matrevials, MPC modified acryl IOL material showed more polynuclear giant foreign body cells in the early period than the other two IOL materials. CONCLUSION: MPC surface modification can reduce the foreign body reaction of IOLs and has the potential to improve biocompatibility of IOL materials.     

氟-肝素表面修饰人工晶状体植入兔眼后眼前段超微结构的改变

目的 探讨兔眼植入著者研制的氟-肝素表面修饰人工晶状体的生物相容性.方法 PMMA及氟-肝素修饰人工晶状体各32枚分别植入兔眼内,术后不同时期处死动物,取眼前段标本进行电镜观察.结果 PMMA人工晶状体组角膜实质出现小局灶性水肿,该处胶原纤维松散,有活跃的巨噬细胞及浆细胞,并有角膜内皮细胞粗面内质网中度扩张;睫状体间质细胞浸润较多,胶原纤维不规则,还有成纤维细胞分布其间.而氟-肝素修饰组,则有较轻的反应.结论 氟-肝素修饰人工晶状体略有较好的生物相容性.     

Biological compatibility of polymethyl methacrylate, hydrophilic acrylic and hydrophobic acrylic intraocular lenses

PURPOSE: Extensive clinical investigations of the biocompatibility of different intraocular lenses (IOLs) have been made in an effort to optimize the outcome of modern cataract surgery. The aim of this study was to add animal eye experimental implantation data regarding cellular reaction on the anterior surface of IOLs. METHODS: Thirteen adult albino rabbits had phacoemulsification/aspiration of the crystalline lens followed by implantation of a posterior chamber IOL in each eye. Three types of IOLs were studied: Hydroview (Bausch and Lomb; n = 7), Acrysof (Alcon, USA; n = 7), and polymethyl methacrylate (PMMA; HOYA, Japan; n = 7). The animals were killed by intravenous pentobarbital 1, 4, or 8 weeks later. The IOLs were explanted and stained with hematoxylin and eosin, and observed under a light microscope. The shape of mouse ascites-induced macrophages on the anterior surface of the three different IOL types (Hydroview, PMMA, and Acrysof) was studied after 24 h of oven culture. RESULTS: Hydrophilic acrylic IOLs showed the highest affinity for lens epithelial cell (LEC) outgrowth, and the lowest and slowest maturation rate reaction of macrophages. PMMA IOLs showed the lowest affinity for LEC outgrowth, and the highest reaction of macrophages. Hydrophobic acrylic IOLs showed intermediate results both regarding LECs and macrophages. CONCLUSIONS: Results suggest that IOL biomaterial properties are the key factor that influences the quantity of monocytes/macrophages as well as the process of their maturation/senescence. LEC outgrowth is influenced both by the biomaterial of IOLs and by the monocyte/macrophage reaction.     

人工晶体表面细胞学反应实验研究

目的观察兔眼后房型人工晶体植人术后人工晶体表面细胞学反应的病变特征及规律，探讨术后眼内炎症反应的发生机理。方法９只青紫蓝兔分为３组。后房型人工晶体植人术后１、７、１４天摘除人工晶体，行光镜和扫描电镜检查，计数炎性细胞数，采用ＳＡＳ软件包，对统计资料做方差分析。结果术后人工晶休表面有明显的炎性细胞；描述了巨噬细胞演变为上皮样细胞、纤维母细胞样细胞和成纤维细胞的过程；首先发现纤维母细胞佯细胞、上皮样细胞与巨噬细胞胞浆内均含有吞噬颗粒，结论推测人工晶体表面的巨噬细胞、纤维母细胞样细胞和上皮详细胞具有效强的吞噬能力，人工晶体表面存在的淋巴细胞群、巨噬细胞和嗜酸性粒细胞提示对人工晶体所在抗原的兔疫反应。     

Deposition of extracellular matrix on silicone intraocular lens implants in rabbits

Purpose: To examine the deposition of extracellullar matrix on silicone intraocular lenses (IOLs) implanted experimentally into rabbit eyes by electron microscopy and to determine the immunolocalization of extracellular matrix components, including collagen types and cellular fibronectin, on these IOLs. Methods: We performed phacoemulsification and aspiration of the crystalline lens and implanted a foldable silicone IOL in the capsular bag of one eye of each of 26 adult albino rabbits under general anesthesia. After 8 weeks the animals were killed and the eyes were enucleated. The silicone IOLs were processed for electron microscopy and for immunohistochemical detection of collagen types I, III, and IV and cellular fibronectin. Results: Electron microscopy revealed deposition of a presumed cell matrix complex on the optic portion of all silicone IOLs, as well as the adhesion of presumed macrophages and foreign-body giant cells. Cellular deposits showed immunoreactivity for cellular fibronectin. Fibrous or membranous deposits exhibited immunoreactivity for cellular fibronectin and collagen types I and III. A few type IV collagen-immunoreactive deposits were also seen. Conclusion: Deposits of extracellular matrix components were observed on silicone IOLs. These deposits may form the scaffolding for the adhesion and proliferation of cells. These matrix components appeared to be the products of cells adhering to the surfaces of IOLs, including lens epithelial cells, macrophages and foreign-body giant cells, indicating that the process of granulation was incomplete.     

Deposition of extracellular matrix on intraocular lenses in rabbits: An immunohistochemical and transmission electron microscopic study

Background: We examined by transmission electron microscopy the accumulation of extracellular matrix on intraocular lenses (IOLs) implanted experimentally into rabbit eyes, and evaluated the immunolocalization of such extracellular matrix components as collagen types I, III, and IV, and cellular fibronectin on these IOLs. Methods: Phacoemulsification and aspiration of the crystalline lens were performed and an IOL was implanted into the capsular bag of each eye of each of 16 adult albino rabbits under general anesthesia. After up to 12 weeks, the animals were killed and the IOLs were removed. Specimens were processed for transmission electron microscopy or for immunohistochemical detection collagen types I, III, and IV, and cellular fibronectin. Results: Transmission electron microscopy revealed an accumulation of extracellular matrix between the residual anterior lens capsule and the surface of an IOL explanted 4 weeks after surgery. Collagen types I and III and cellular fibronectin were detected immunohistochemically on each IOL in association with cellular deposits. Type IV collagen-immunoreactive matrix was not seen on the optic portion, but was detected on the haptic portion of one of six IOLs examined. Conclusion: Each component of the extracellular matrix that is deposited on the IOL supplies scaffolding for the adhesion and proliferation of cells. These components are considered to be produced by cells such as lens epithelial cells and macrophages that adhere to the IOL surface.Presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology at Fort Lauderdale, Florida, USA on 15 May 1995 at the Quintessence of Ophthalmology Meeting in Sopron, Hungary, on 6 October 1995     

Pathology and general significance of fibrin deposition on lens implants

The deposition of fibrin on the intraocular lens (IOL) in two cases of failed implantation is reported. In one case the network of fibrin fibers was isolated on the surface of an IOL that also showed a clear reactive protein film populated by macrophages and giant cells. In the other case the fibrin network was closely related to sessile macrophages on the implant surface. The presence of fibrin on IOLs indicates an acute phase of increased regional vascular permeability and is clinically important.     

Collagenous deposits on explanted intraocular lenses.

An immunohistochemical study of type I collagen in deposits on the surface of two intraocular lenses (IOLs) explanted from human eyes was conducted. Type I collagen-immunoreactive proteinaceous deposits with cells were found around the haptics of an iris-supported IOL. A few such deposits and what appeared to be macrophages were observed on the optic. A few cells (presumably macrophages and giant cells) were observed on a posterior chamber IOL, whereas proteinaceous deposits that reacted positively to the antibody were not identified. Type I collagen-immunoreactive deposits on the iris-supported IOL were thought to be the products of fibroblastic cells, originating from iris tissue, that attached directly to the haptics and helped stabilize the implant.     

Immunohistochemical study of cellular response on the intraocular lens surface

This immunohistochemical study was conducted to observe the cellular proliferation on the surface of an intraocular lens (IOL) implanted in the rabbit eye. One week after extracapsular lens extraction followed by posterior chamber lens implantation, the IOL was removed and examined by an indirect immunohistochemical method using anti-macrophage antiserum. Macrophage immunoreactivities were observed on the small round cells, the middle-sized oval cells, the foreign-body giant cells and the fibroblast-like cells attached to the surface of the IOL. Most of the cellular components on the implanted IOL seemed to be macrophages.     

Improved biocompatibility of intraocular lenses by heparin surface modification: a 12-month implantation study in monkeys

To evaluate the long-term biocompatibility and potential side effects of heparin surface modification of a poly(methyl methacrylate) intraocular lens (IOL), a heparin surface modified IOL was implanted in the left posterior chamber of 24 cynomolgus monkeys and a reference IOL (without surface modification) was implanted in the right eye in 12 of these animals. Twelve eyes were not operated on. Eleven eyes in seven monkeys were lens extracted as a control of the surgical method. Slitlamp examinations and intraocular pressure recordings were made one day, one and two weeks, and 1, 2, 2 1/2, 3 1/2, 6, 8, 10, and 12 months after the operation. Eleven monkeys were sacrificed after 3 1/2 months and the remaining animals after 12 months for morphological examination of the eyes. Slitlamp and morphological examinations showed that cell deposits, pigmentation, and posterior synechias were significantly less in eyes with heparin surface modified IOLs than in eyes with reference IOLs throughout the 12-month observation period. The intraocular pressure was equally reduced in eyes with heparin surface modified IOLs and reference IOLs for about one month, after which it returned to normal. No side effects following the implantation of heparin surface modified IOLs were observed. We concluded that heparin surface modification of IOLs is efficient for long-term reduction of cell deposits and posterior synechias after implantation in monkey eyes and may also be effective in lowering the degree of side effects to IOL implantation in humans.     

Influence of fibronectin on the adherence of Staphylococcus epidermidis to coated and uncoated intraocular lenses

PURPOSE: To determine the effect of the modification of intraocular lens (IOL) surface properties on the adhesion of Staphylococcus epidermidis caused by fibronectin (FN) as the predominant proadhesive glycoprotein of the eye's initial foreign body reaction. SETTING: University of Saarland, Homburg/Saar, Germany. METHODS: Eleven IOL types were tested. The IOLs were of poly(methyl methacrylate), acrylate, or silicone. Some were surface modified with heparin or polysaccharide coating. The IOLs, unadsorbed or preadsorbed with fibronectin (FN), were incubated with [(3)H]-thymidine-labeled S epidermidis Rp62a, and the amount of adherent microorganisms was determined. RESULTS: Attachment of S epidermidis adhesion to various types of IOLs, both unadsorbed and FN precoated, varied significantly. The attachment to highly adhesive IOLs was almost 4-fold greater than that to low-adhesive IOLs. Attachment to FN precoated IOLs was generally enhanced compared with attachment to unadsorbed IOLs. Heparin surface modification resulted in no or a modest reduction in bacterial adhesion compared with unmodified IOLs. Bacterial adhesion was highly statistically significantly less on IOLs with polysaccharide surface modification. CONCLUSIONS: There was significant variability in S epidermidis adhesion to IOLs as a function of design, material, surface modification, and FN preadsorption. Application of the findings may foster new developments to further reduce the major complication in cataract surgery, infective endophthalmitis.     

Impact of fibronectin on surface properties of intraocular lenses

Purpose  Physical properties of intraocular lens (IOL) surfaces determine biocompatibility. IOL hydrophobicity of commercially available IOLs with and without fibronectin (FN) coating can be determined by surface contact angle (SCA) measurements. SCA data of IOLs may allow for a rational selection of an IOL type as a function of underlying eye disease. Setting  University Hospital of Saarland, Homburg (Saar), Germany Methods  Thirteen IOL types were tested. IOLs were made of poly(methyl methacrylate)(PMMA), acrylate, or silicone. Select IOLs were surface modified by the manufacturer with heparin or a polysaccharide coating. SCA values of IOLs, either uncoated or precoated with FN, were determined using the sessile water drop method. Results  SCA values ranged from 61.3 to 116.1° for unmodified IOLs, with PMMA IOLs being more hydrophilic (median SCA, 74.1°), silicone IOLs more hydrophobic (median SCA, 113.3°), and acrylate IOLs intermediate (median SCA, 86.6°). Upon FN coating, all genuine acrylate lenses became significantly more hydrophilic while this effect was either nonsignificant or opposite on some PMMA and silicon IOLs. Heparin or polysaccharide surface modification resulted in significantly reduced SCA values. On acrylate IOLs, SCA values did not correlate with the aqueous content of the material. Conclusions  This study associates IOL materials, surface modifications, and the role of FN preadsorption with SCA values reflecting surface hydrophobicity versus hydrophilicity. It provides a rationale for specific IOL selection as a function of the clinical setting, and a basis for IOL development using tailored surface physicochemistry to enhance biocompatibility and to reduce susceptibility to implant infection. Financial disclosure  None of the authors has a commercial or proprietary interest in any of the products discussed in this article.