by Noelle La Croix, DVM, Dip. ACVO
The ocular surface is compromised of the cornea, conjunctiva, and the tear film. The cornea’s glucose, electrolytes, and amino acids are supplied by the aqueous humor. Corneal vitamins, growth factors, protease inhibitors, and neuropeptides are provided by lacrimal gland secretions. Following ocular trauma and/or inflammation, conjunctival vessels release complement and antimicrobial factors (lactoferrin and immunoglobulins) as well as adhesive fibronectin into the tear film. Subsequently, tears can provide epitheliotropic and antimicrobial properties in addition to lubrication. Various ocular diseases can affect adversely affect these functions of the tear film. Ocular medications, sera, plasma, and platelet-rich plasma have been used to restore and/or supplement the healing properties provided by the tear film. This article will explore the use of blood derived products in promoting corneal health.
Matrix metalloproteases proteases (MMPs) 2 and 9 are important enzymes that help degrade diseased or dead corneal tissue encouraging corneal remodeling. In a healthy cornea MMP2, but not MMP9, is found within the corneal epithelium. In a diseased cornea levels of MMP2 are elevated above normal and significant amounts of MMP9 are produced by keratocytes, corneal epithelia, and polymorphonuclear cells. Bacteria infecting a cornea may produce additional degradative proteases. Both sera and plasma contain protease inhibiting alpha macroglobulin. Alpha macroglobulin binds to, and is subsequently cleaved by, many proteases. Cleaved alpha macroglobulin then collapses around an active site of a protease sterically shielding it from further protease activity. Topically applied sera or plasma can therefore significantly retard corneal degradation.
There are other benefits to the topical application of sera or plasma to an unhealthy corneal surface. These effects are mainly due to increased concentrations of neuropeptides, growth factors, and vitamins in these blood products when compared with levels in normal tears. Blood factors including epidermal growth factor (EGF), transforming growth factor beta (TGF-beta), fibronectin, and substance P promote the migration and adhesion of corneal epithelia driving both stromal and epithelial repair. Sera and plasma also contain bacteriocidal/bacteriostatic immunoglobulins, and vitamin A that discourages corneal squamous metaplasia.
Both sera and plasma from dogs, cats, and horses has been shown to equally prevent corneal malacia. In humans, sera outperform plasma in epithelial trophic capabilities. Human sera are more enriched than plasma in EGF, platelet derived growth factor (PDGF), TGF-beta, and vitamin A. These growth factors found in human sera derive from clotting platelets. Human sera are more stimulating than plasma for cell growth, migration, and differentiation.
To further increase the concentration of healing growth factors, human medicine has developed platelet-rich plasma (PRP). Plasma is first centrifuged to isolate the buffy coat which is additionally centrifuged to separate white blood cells from the remaining PRP. This PRP has higher concentrations of EGF, TGF beta, and PDGF when compared with traditional sera or plasma. It has been found that PRP highly stimulates corneal cell proliferation, but corneal cell migration and differentiation are better stimulated by sera. Further research is needed to see if PRP will have similar effects in veterinary patients. Unfortunately, current protocols for generating PRP require a large volume of blood (at least 30 milliliters). This volume may be difficult or impractical to obtain from small animals.
At this point in time, veterinary ophthalmologists typically choose to stimulate corneal health by topical application of patient-derived serum. For small (low blood volume) patients, sera may be harvested from donor animals. Owners are instructed to refrigerate sera and to discard unused portions within one week of its initial drawing. If you have any further questions regarding the topical corneal application of sera and plasma, please feel free to consult with your veterinary ophthalmologist.
Noelle La Croix, DVM, Dip. ACVO
Veterinary Medical Center of Long Island
75 Sunrise Highway
West Islip, New York 11795
(631) 587-0800; fax (631) 587-2006