Fibronectin may be responsible for attachment of acrylate IOLs to the capsular bag, study says

Plausible reason for less PCO and lower YAG rates observed with the AcrySof.

Issue: October 1, 2000

ByBob Kronemyer

VAASA, Finland - A study evaluating adhesion of fibronectin, vitronectin, laminin and collagen type IV to various IOL materials in pseudophakic human autopsy eyes suggests that fibronectin may be the major extracellular protein responsible for attachment of acrylate IOLs to the capsular bag.

"If an IOL binds more fibronectin, vitronectin or laminin, it might have a better ability to attach to the posterior capsule," said investigator Reijo J. Linnola, MD, an ophthalmologist in practice here.

Dr. Linnola divided his presentation at the American Society of Cataract and Refractive Surgery annual meeting into two sections: histology and explanted lenses. The study was conducted at the Storm Eye Institute in Charleston, S.C.

The investigators studied 38 autopsy eyes that had IOLs: 14 acrylic AcrySof (Alcon, Ft. Worth, Texas), 10 PMMA, 10 silicone and four hydrogel lenses. "These eyes were embedded in paraffin, and histological sections were made," Dr. Linnola said. "From histological sections, immunohistochemical sections for detecting fibronectin, laminin, vitronectin and collagen type IV were made." In total, 152 immunohistochemical sections were evaluated.

Fibronectin dominant

---Immunohistochemical staining for fibronectin (in red). At the back of the anterior capsule one can see a layer of fibronectin, which was between the AcrySof IOL and the capsule, with only some lens epithelial cells. The IOL was detached from the capsule during preparation of the specimen.

Between the anterior or posterior capsule and the AcrySof, "you can see a layer of protein in between the capsule and the lens surface," Dr. Linnola said (see figures 1 and 2). "This protein layer stains for fibronectin. And there are only some lens epithelial cells that can be seen here." For the PMMA IOL sections, "we can see that vitronectin and laminin are involved in the process. But these proteins are not lining the tissues against the IOL surface, so, probably, they are not involved in the adhesion of the capsule to the IOL surface." Still, "when you look at this sample with fibronectin staining and at higher magnification, you can see that there is fibronectin lining the tissue against the IOL surface [see figure 3]. However, the adhesion of this tissue to the PMMA IOL has been loose or non-existent because a multiple layer of lens epithelial cells has been allowed to grow."

Silicone lenses reacted differently. "Vitronectin and laminin are inside the fibrocellular tissue responsible for the posterior opacification, but the tissue is lined with collagen type IV against the IOL," Dr. Linnola said. "A thick, secondary cataract has developed, and it is lined with collagen type IV, as if the IOL would have been encapsulated in the capsular bag with collagen type IV, not attached to it" (see figure 4).

In short, there was "a significant difference in fibronectin adhesion to soft hydrophobic acrylate IOLs. More fibronectin was attached to them," Dr. Linnola said. "This kind of structure was observed significantly more often with the AcrySof IOLs than with the PMMA, silicone or hydrogel lenses." Laminin or vitronectin did not directly line the fibrocellular tissue to any of the IOL surfaces.

Sandwich theory

---Immunohistochemical staining for fibronectin. The AcrySof IOL posterior surface is above, the posterior capsule below. Between them there is a layer of protein, which has been stained for fibronectin. Fibronectin seems to be capable of producing a bioactive bond between the soft hydrophobic acrylate of AcrySof and the collagenous capsule.

This first section of the study appears to "confirm the sandwich theory [see sidebar] for posterior capsule opacification," Dr. Linnola said. "Besides its square-edged optic, the AcrySof IOL significantly more often had this kind of structure: capsule, fibronectin, lens epithelial cell layer, fibronectin, IOL surface." With collagenous capsule fibronectin, a bioactive bond is produced, "and thus attaches the hydrophobic acrylate IOL to the capsule. This may explain why we see lower YAG rates with the AcrySof," he said.

The explanted IOL section of the study consisted of 32 human autopsy eyes with IOLs: 13 AcrySof, nine silicone, eight PMMA and two hydrogel lenses. Like the histological examination, the surface of the IOL was immunohistochemically stained for detection of fibronectin, laminin, vitronectin and collagen type IV. IOL surfaces were also analyzed for presence of epithelial cells.

When staining for fibronectin, "we saw more fibronectin attached to the AcrySof surface," Dr. Linnola said (see figure 5). "We could see that fibronectin had been present in the area where the anterior capsule had covered the IOL surface." In contrast, "there was little fibronectin on the PMMA IOLs and nearly none on the silicone or hydrogel lenses."

On the other hand, there was more collagen type IV attached to the silicone lenses compared to the AcrySof or PMMA lenses. But silicone IOLs did not have any vitronectin on their surfaces. "A little was attached to the PMMA IOL surface, but a lot more could be seen on the AcrySof," Dr. Linnola said. Also, no significant differences in laminin were seen between the three lens groups.

Cell count

---Posterior capsule opacification with PMMA IOL seen here, as a multiple layer of lens epithelial cells with extracellular matrix proteins over the wrinkled posterior capsule. Immunohistochemical staining for fibronectin (in red).

Nonetheless, more epithelial cells were attached to acrylic IOLs than to PMMA or silicone lenses. "More cells were also attached to PMMA IOLs than to silicone IOLs," Dr. Linnola said.

Dr. Linnola said that both the histological and explant IOL sections of his study supported the hypothesis that there is better adhesion of fibronectin to soft acrylic, hydrophobic acrylate AcrySof IOLs. "This suggests that fibronectin could be the mediator of this bioactive bond between the IOL and the posterior capsule," he said.

In plastic-embedded histological specimens, "we have seen AcrySof IOLs shrink-wrapped in the capsular bag," Dr. Linnola said. "I believe the beginning of this whole process is the adhesion with proteins, which then provides the capsule an opportunity to produce a wrapped system around the IOL. So, it is not shrink-wrapping itself that is doing the adhesion. First comes the adhesion." Dr. Linnola said that fibronectin first appears after the blood-aqueous barrier is broken as a result of surgery. "We have fibronectin in our blood circulation all the time. So, it is available in the first hour or so of surgery."

More extensive secondary cataract formation over the posterior capsule with a silicone IOL. Immunohistochemical staining for collagen type 4 (in red).

The explanted AcrySof IOL shows adhesion of fibronectin on its surface (in red).

The Sandwich Theory

Phase 1. The anterior capsule over the bioactive surface of the IOL bonds directly with or through the remaining lens epithelial cells to the IOL. The IOL and the capsular bag form a closed system. Inside the bag the remaining lens epithelial cells proliferate and migrate behind the IOL. A 90° edge of the IOL optic against the posterior capsule can now direct the lens epithelial cells to proliferate as a monolayer of cells between the IOL and the posterior capsule.

Phase 2. The bioactive bond is formed when a single lens epithelial cell has the posterior capsule on one side and the bioactive IOL surface on the other side. The sandwich is formed, and the cell-posterior capsule junction and the cell-bioactive IOL surface junction prevent more cells from migrating behind the IOL. The posterior capsule remains clear.

Phase 3. After some time, a part of these monolayer cells will die. The reason may be aging of the patient, lack of nutrition or the pressure effect of the IOL against the posterior capsule. A true contact with the IOL and the posterior capsule is formed in these places.

For Your Information:

Reijo J. Linnola, MD, can be reached at Saratie 16 D, 65280 Vaasa, Finland. (358) 40 530 6000; fax: (358) 6 321 6689; e-mail: reijo.linnola@pp.qnet.fi. Dr. Linnola does not have a direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any company mentioned in this article.

Alcon can be reached at 6201 South Freeway, Fort Worth, TX 76134; (800) 862-5266; fax: (847) 241-0677.