Abstract
Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation.
Highlights
There are a number of stem niches in ocular tissue that are vital to maintenance, repair and regeneration [1]; these include limbal stem cells (LSCs)
It has been suggested that growth factors and cytokines secreted by epithelial cells regulate keratocyte cell function and vice versa [46,65] in a reciprocal bidirectional manner that aid and stimulate normal migration and the secretion of proteoglycans and glycoaminoproteins in a simultaneous, highly coordinated manner which changes dependent upon development, homeostasis and wound healing; direct cell-cell communications do occur in some situations [128] that are vital to cell response [54]
The cornea is capable of restoring full function via a regenerative approach and one of the most demanding challenges in corneal biology is in the assistance of tissue repair via regeneration as opposed to fibrosis
Summary
Vision is reliant upon the discrete organization, structure and functional integration [1] of the corneal stroma and its components. It is made up of closely interdigitated cells arranged in a mosaic pattern of mostly hexagonal shapes [11] It is essential for keeping the cornea clear as it pumps excess fluid out of the stroma. Corneal transparency is heavily dependent upon the highly complex levels of organization and regular spatial order of the thin collagen fibrils within the stromal layer [3,16,17]. Electron microscopy and X-ray diffraction studies [25] indicate that the fibrils in adjacent stromal lamellae are predominantly orthogonal in arrangement [26] It is the nanoscale organization of the stromal layer that is responsible for the corneas strength, clarity and its ability to refract light. It is the principle reason why tissue engineered corneas have far failed to reach the clinic [1]
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