The cornea is one of the most significant refractive components of the visual system which plays a crucial role in vision by focusing light onto the retina. The corneal stroma constitutes around 90% of corneal thickness and maintains optical transparency due to uniform interfibrillar distance and unique collagen fibril arrangement [1]. Most corneal diseases including infection, immune disorders, chronic inflammation, and mechanical or chemical trauma involve the stroma and trigger corneal wound healing response. In severe response, these ocular disorders tend to cause severe inflammation, neovascularization, and disruption in the stromal organization, which can all lead to corneal opacity and eventually permanent vision loss [2].

Corneal opacities are a major cause of vision loss worldwide [3]. However, the current therapies including lubrication, antibiotics, steroids, or amniotic membrane grafting are suboptimal to manage the corneal wound healing process [4]. The most common and effective intervention for restoring corneal clarity is corneal transplantation. However, there are major drawbacks related to the limited supply of donor tissue, and postoperative issues such as immune reactions, transplant rejection, cataract and/or glaucoma [5].

Therefore, there is an obvious need to develop new treatment strategies that are efficient in promoting wound healing in patients with severe corneal disorders. One of the tremendous efforts is mesenchymal stem cell (MSC)-based regenerative therapies which are under investigation to reduce or eliminate the need for corneal transplantation. Mesenchymal stem cells, a type of multi-potent cell, can be isolated from oral tissue, cord blood, heart tissue, bone marrow, and adipose tissue [6]. The importance of MSCs in tissue healing is well known in almost every branch of medicine [[7], [8], [9]], and recent experimental and clinical studies demonstrate the success of MSCs in restoring the stromal functions and corneal transparency in ocular surface disease including cases of corneal injury [[10], [11], [12], [13]] because of their differentiation potential, anti-inflammatory effects, and most importantly immune-modulating properties [[14], [15], [16]].

In recent years, photobiomodulation (PBM) using low-level light has been also applied in regenerative medicine as it stimulates tissue repair by regulating cellular viability, proliferation and migration, collagen synthesis, and growth factors levels [[17], [18], [19], [20]]. Furthermore, this modality has contributed positively to the tissue repair capacity of MSCs by enhancing their proliferation and immunomodulatory functions [[21], [22], [23]]. In PBM, photons in the visible (390–700 nm) and near-infrared (NIR, 780–1200 nm) spectrum are absorbed by mitochondria, and then the production of ATP and nitric oxide is elevated, which improves cellular functions [24]. There are several studies reporting the benefit of PBM in retinal injury and retinal degenerative disease [25,26]; however, few studies focus on the effects of PBM on ocular surface diseases and corneal injury [[27], [28], [29]]. In these studies, which investigated the effect of low-level laser therapy on corneal epithelial healing [ 27], dry eye treatment [28], and corneal healing response in the alkaline burn [29], different wavelengths of NIR light (740 nm or 810 nm) were used, and there is still a lack of consensus regarding the standard treatment parameters in light therapy. Therefore, we preferred to use polychromatic light with a broader spectrum of wavelengths, including NIR wavelengths in our study to maximize therapeutic efficacy. To our knowledge, this is the first study to investigate the effects of light on mechanically damaged corneas.

We hypothesized that combining adipose-derived MSCs (ADMSCs) therapy with PBM could enhance the therapeutic effects compared to either ADMSCs or PBM alone. In this study, we investigated and compared the efficacy of ADMSCs and PBM with polychromatic light in the NIR, alone and in combination, on corneal opacity, inflammatory response, and tissue architecture in a rat corneal opacity model created by mechanical injury.