Progressive nonulcerative paracentral keratolysis associated with elevated corneal metalloproteinases.

Purpose: We report a patient with progressive idiopathic, nonulcerative, noninflammatory, avascular, bilateral, paracentral and peripheral corneal thinning monitored for 13 years.

Methods: Because of progressive corneal thinning, the patient underwent several surgical procedures, including an arcuate lamellar keratectomy with suturing, bilateral 15-mm diameter onlay lamellar corneoscleral epikeratoplasties, and removal of interface epithelial tissue. Over time, the keratolysis also thinned the donor stroma, requiring a lamellar tectonic graft.

Synthetic epikeratoplasty in rhesus monkeys with human type IV collagen.

Human type IV collagen discs were found to support proliferation and adhesion of rabbit corneal epithelial cells in tissue culture. To assess the biocompatibility of this synthetic collagen for epikeratoplasty, seven eyes of seven rhesus monkeys underwent epikeratoplasty with lenticules made of human type IV collagen. Eye rubbing by the animals expulsed two of the lenticules and caused failure of two to epithelialize completely.

Changes in the nuclear structure in the radiation-sensitive CHO mutant cell, xrs-5.

The structural organization of the cell nucleus was investigated by transmission electron microscopy in the radiosensitive Chinese hamster ovary (CHO) cell mutant, xrs-5 (D0 = 45 cGy), relative to parental K1 cells (D0 = 200 cGy). In 99% of all xrs-5 cells, the outer layer of the nuclear envelope was separated from the inner layer, while 96% of K1 cells had closely apposed layers. This separation of the inner and outer layers of the nuclear envelope in xrs-5 cells was not explained by an increased susceptibility of xrs-5 cells to osmotically induced changes because (1) xrs-5 cells retained the altered nuclear periphery even when several different fixation protocols were used and (2) xrs-5 cells were not more susceptible to cell lysis as measured by trypan blue dye exclusion or by the extracellular presence of lactate dehydrogenase.

Current status of synthetic epikeratoplasty.

Many of the deficiencies with human tissue epikeratoplasty might be improved by the use of a suitable synthetic lenticule. Potential biomaterials for epikeratoplasty include collagen (types I, III, or IV), collagen-hydrogel copolymers, bioactive synthetics, and coated hydrogels. The biomaterial must be engineered to achieve strict specifications of optical clarity, support of epithelial migration and adhesion, permeability to solutes, and stability to corneal proteases.

Collagenase secretion accompanying changes in cell shape occurs only in the presence of a biologically active cytokine.

We have investigated the relationship between collagenase production, cell shape and stimulatory factors in cell culture. In a homogeneous culture of primary rabbit corneal stromal cells, shape change induced by a variety of agents was not effective in stimulating collagenase secretion. Only in the presence of a biologically active cytokine or phorbol myristate acetate was a correlation seen between changes in cell shape (induced by a second agent) and collagenase secretion by these primary cells.

Regenerate epithelium and skin glands of the adult newt react to the same monoclonal antibody.

A search for specific proteins involved in newt limb regeneration, using monoclonal antibodies against forelimb blastemas, led to the detection of an antigen in the regenerate epithelium. Fluorescent-antibody-labeled cells first appeared just prior to blastema outgrowth. From bud through early digit stages this antibody reacted with nearly all of the regenerate epithelial cells.

Stimulation of collagenase synthesis by a 20,000-dalton epithelial cytokine. Evidence for pretranslational regulation.

Certain products of cultured rabbit corneal epithelium or epidermis regulate collagenase production by rabbit corneal stromal cells. Here, we examined the effects of a 20-kDa cytokine derived from cultured epithelium on collagenase expression by normal human skin fibroblasts and by cells from recessive dystrophic epidermolysis bullosa, a disease characterized by over-production of a structurally altered collagenase. Culturing cells for 24 h in the presence of the cytokine resulted in an approximately 2-fold increase in trypsin-activatable collagenase activity paralleled by an increase in immunoreactive protein, suggesting enhanced synthesis.

Organization of collagen types I and V in the embryonic chicken cornea: monoclonal antibody studies.

To determine whether type V collagen is antigenically masked in situ by its fibrillar organization, two different methods were used to perturb selectively the structure of collagen fibrils in sections of embryonic chicken corneas. The experimentally modified tissues were probed by immunohistochemical procedures with monoclonal antibodies against types V and I. A lathyritic agent was used to block crosslinking of newly synthesized collagen.

Regulation of connective tissue collagenase production: stimulators from adult and fetal epidermal cells.

We have examined the ability of primary adult rabbit skin cells to regulate collagenase production in vitro. Dermal cells constitutively produce collagenase in culture, and enzyme production by these cells can be influenced by epithelial cells. Co-culture with skin epidermal cells resulted in more enzyme production by dermal cells, whereas co-culture with corneal epithelial cells yielded less enzyme activity.

Regulation of stromal cell collagenase production in adult rabbit cornea: in vitro stimulation and inhibition by epithelial cell products.

Media conditioned by epithelial cells from the adult rabbit cornea were capable of both stimulating and inhibiting production of latent collagenase by stromal cells from the same source. Cytochalasin B was required in this in vitro system for both secretion of stimulators by epithelial cells and production of collagenase by stromal cells in response. Optimal production of collagenase by stromal cells in response.