Keratoconjunctivitis sicca (KCS), also known as “dry eye syndrome,” is a common ocular disease in dogs resulting from lacrimal gland (LG) inflammation and decreased tear production. KCS can occur either as a quantitative deficiency in the aqueous component of tears or as a qualitative deficiency in the lipid or mucin layers of the tear film, causing tear film instability, with potential damage to the ocular surface1. This damage is characterized by the presence of mucoid ocular discharge, conjunctival hyperemia, blepharospasm, recurrent corneal ulceration, corneal vascularization, fibrosis, and, eventually, corneal pigmentation. In severe cases, dense corneal opacification (clouding) or corneal perforation secondary to deep ulceration can lead to blindness or even loss of the eye2–4. The diagnosis of quantitative KCS is based on typical ocular surface changes, as well as on dysfunction in tear production, which is evaluated by biomicroscopy of the anterior segment and by the Schirmer tear test (STT), respectively. The STT determines whether the eye produces enough tears to keep it moist and ranges from normal (15–25 mm/min), mild (9–14 mm/min), moderate (>4 to 8 mm/min), to severe (≤4 mm/min)3.

Any condition that impairs the ability to produce adequate amounts of tear film can result in KCS2. Local immune-mediated disease is the most widely accepted cause of KCS based on histopathology of tear-producing glands and on the clinical response to immunomodulators2,5,6. However, other systemic diseases may also be associated with KCS, such as infection with canine distemper virus, hypothyroidism, diabetes mellitus, and Cushing’s disease7. In addition, systemic administration of pharmaceutical agents for long periods and at high doses has also been reported to cause dry eye8. The most common treatment for KCS is the prescription of immunosuppressive drugs, such as cyclosporine and tacrolimus, which may need to be used indefinitely9. Furthermore, some authors believe a small number of dogs are resistant to the action of cyclosporine10. It is important to explain to the owner that the dog with KCS needs constant care, such as removal of secretions from around the eyes many times a day to minimize irritation of the eyelids, conjunctiva, and cornea. Thus, efforts are being made to develop alternative therapies to inhibit the immune response and inflammatory processes in order to reduce the suffering of animals with KCS and the need for their constant care.

It is known that mesenchymal stem cells (MSCs) are powerful regulators of the immune response and that they have been shown to be effective in treating various immune disorders in human and animal models11–19. Previous studies have already demonstrated safety aspects of MSC transplantation into the LG and tear production improvement after MSC transplantation in dogs with KCS20–22. However, it remains unclear whether MSC transplantation is efficient and leads to a good prognosis—tear production levels reverting to normal—in cases of severe KCS, especially in the long term. We thereby carried out the present study to evaluate the effects of MSC transplantation into LGs on tear production and clinical signs in dogs with mild–moderate versus severe KCS.

Veterinary patients, such as dogs, are increasingly recognized as critical translational models of human diseases because the etiopathogenesis of canine diseases is similar to that of humans23, particlularly regarding Sjögren’s syndrome24,25. Sjögren’s syndrome is a systemic autoimmune disease diagnosed by its two most common symptoms—dry eyes and dry mouth24. For this reason, canine KCS studies may aid in the development of therapeutic interventions that can benefit humans. Over the last few years, there has been an increase in the demand for sophisticated therapies, such as the use of stem cells, in animal companion care, which has led to a surge in stem cell studies using dogs26. These studies should provide a unique opportunity for assessing both efficacy and safety of human adult stem cell therapies that can be translated to human medicine.

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