https://www.jbc.org/content/278/46/45629.full.pdf

Keratocyte Phenotype Mediates Proteoglycan Structure A ROLE FOR FIBROBLASTS IN CORNEAL FIBROSIS

Distribution of Proteoglycans Antigenically Related to Corneal Keratan Sulfate Proteoglycan

The cornea of the eye is a unique, transparent connective tissue. It is comprised predominantly of collagen fibrils, remarkably uniform in diameter and regularly spaced, organized into an intricate lamellar array. Its establishment involves a precisely controlled sequence of developmental events in which the embryonic cornea undergoes major structural transformations that ultimately determine tissue form and function. In this article, we will review corneal developmental dynamics from a structural perspective, consider the roles and interrelationships of collagens and proteoglycans, and comment on contemporary concepts and current challenges pertinent to developmental processes that result in an optically clear, mature cornea.

Development of the corneal stroma, and the collagen–proteoglycan associations that help define its structure and function

Proteoglycan molecules in keratoconus corneas were studied by immunohistochemical and electron microscopic histochemical methods. Compared with normal human control subjects, the staining intensity with monoclonal antibody 9-A-2 was enhanced in the stroma of scarred keratoconus corneas, whereas the intensity with antibody J-19 was reduced. The 9-A-2 experiment showed an increased immunoreactivity of dermatan sulfate proteoglycan epitopes, and the J-19 experiment indicated a decreased immunoreactivity of sulfated keratan sulfate epitopes. Uronic acid analyses were consistent with the 9-A-2 data. Electron microscopy performed after cuprolinic blue staining showed apparent accumulation of abnormally thick, chondroitinase ABC-sensitive, dermatan sulfate proteoglycan filaments in keratoconus corneas. Such filaments were especially prominent in scarred areas. In addition, Keratan sulfate proteoglycan filaments appeared to be less abundant than those found in normal control corneas. Similar alterations of both types of proteoglycan molecules were also seen and reported in scarred corneas. The similarity suggests that the proteoglycan abnormalities found in keratoconus corneas may be secondary, at least in part, to scarring.

Proteoglycan molecules in keratoconus corneas.

Immunohistochemical Evidence of Heterogeneity in Macular Corneal Dystrophy

Twenty-six monoclonal antibodies (MAbs) developed against rabbit corneal proteokeratan sulfate (PKS), were used to evaluate immunohistochemically the ocular distribution of PKS during prenatal and early postnatal development in rabbits These MAbs were directed against epitopes located in the keratan sulfate (KS) chains of the proteoglycan (SundarRaj et al, 1985) Staining of cryostat sections of the eyes was carried out using an indirect peroxidase-conjugated technique Only one of the MAbs reacted with the presumptive corneal region at day 13 or 16 of fetal development By day 20, more MAbs reacted with the corneal stroma There were distinct differences, however, in the distribution of the epitopes recognized by the various MAbs A few of them stained only the posterior region of the cornea, whereas others showed a decreasing staining gradient from the posterior to the anterior region By day 24, all of the MAbs reacted with the corneal stroma, but some reacted also with the limbal region and with the conjunctival stromal matrix One MAb also reacted with the conjunctival epithelial layer, but only at this stage of development Conjunctival staining was more intense at day 28 of fetal development and at day 2 postnatally KS was not detectable in the conjunctiva of adult rabbits with any of the MABs These results suggest that although KS synthesis starts at very early stages of fetal development, there are progressive changes in its antigenic structure in specific regions of the cornea and conjunctiva during corneal development

Nirmala Sundarraj

Papers

Ocular distribution of keratan sulfates during pre- and postnatal development in rabbits.