The Cornea: No Difference in the Wound Healing Response to Injury Related to Whether, or Not, There's a Bowman's Layer

Abstract

Bowman's layer is an acellular layer in the anterior stroma found in the corneas of humans, most other primates, chickens, and some other species. Many other species, however, including the rabbit, dog, wolf, cat, tiger, and lion, do not have a Bowman's layer. Millions of humans who have had photorefractive keratectomy over the past thirty plus years have had Bowman's layer removed by excimer laser ablation over their central cornea without apparent sequelae. A prior study showed that Bowman's layer does not contribute significantly to mechanical stability within the cornea. Bowman's layer does not have a barrier function, as many cytokines and growth factors, as well as other molecules, such as EBM component perlecan, pass bidirectionally through Bowman's layer in normal corneal functions, and during the response to epithelial scrape injury. We hypothesized that Bowman's layer represents a visible indicator of ongoing cytokine and growth factor-mediated interactions that occur between corneal epithelial cells (and corneal endothelial cells) and stromal keratocytes that maintain the normal corneal tissue organization via negative chemotactic and apoptotic effects of modulators produced by the epithelium on stromal keratocytes. Interleukin-1 alpha, produced constitutively by corneal epithelial cells and endothelial cells, is thought to be one of these cytokines. Bowman's layer is destroyed in corneas with advanced Fuchs' dystrophy or pseudophakic bullous keratopathy when the epithelium becomes edematous and dysfunctional, and fibrovascular tissue commonly develops beneath and/or within the epithelium in these corneas. Bowman's-like layers have been noted to develop surrounding epithelial plugs within the stromal incisions years after radial keratotomy. Although there are species-related differences in corneal wound healing, and even between strains within a species, these differences are not related to the presence or absence of Bowman's layer.

Keywords: Bowman’s layer; TGF beta; corneal fibroblasts; corneal wound healing; epithelial basement membrane; fibrosis; keratocytes; myofibroblasts.

Figure 2

Immunohistochemistry for EBM component perlecan (470 kDa) in the normal unwounded human cornea (A–C) compared to a normal human cornea thirty minutes after epithelial scrape injury (D–F) prior to enucleation for choroidal melanoma. Perlecan produced by the stromal cells penetrates full-thickness Bowman’s layer (area between the two superior and one inferior arrowheads in each panel) either from keratocytes that have upregulated perlecan production (this can be seen throughout stroma in (E,F)) or from the scraped epithelial cells as they were removed, or possibly both, to accumulate at the site of nascent EBM regeneration. Blue is DAPI staining of cell nuclei in all panels. e is epithelium. Mag. 400×. Reprinted with permission from Ref. [41]. Copyright 2015 Experimental Eye Research.

Figure 1

Hematoxylin and eosin staining of an anterior rabbit cornea (A) without Bowman’s layer and a human cornea (B) with Bowman’s layer (arrows). e is epithelium. s is stroma. Mag. 200×.

Figure 3

Bowman’s layer pathology. Bowman’s layer is destroyed in advanced bullous keratopathy when the epithelium becomes dysfunctional due to edema. In this cornea, ectopic fibrous tissue developed beneath the epithelium (arrowheads) and extended into the epithelium (large arrow). Hematoxylin and eosin staining. Mag. 200×. Reprinted with permission from Ref. [12]. Copyright 2020 Experimental Eye Research.