Enhancing Late Retinopathy of Prematurity Outcomes with Fresh Bone Marrow Mononuclear Cells and Melatonin Combination Therapy.

Abstract

Introduction: Retinopathy of prematurity (ROP) is a vasoproliferative disease affecting premature neonates with life-lasting impacts. This study aims to investigate the long-term functional outcomes and alterations in neural retina architecture following the intravitreal transplantation of bone marrow mononuclear cells (BMMNC) in the rat models of ROP, and to evaluate the effect of adjunctive therapy with melatonin.

Methods: 32 neonate rats were employed. The ROP model was developed in 10 neonatal rats, and two were assigned as control. The ROP models received BMMNC suspension, containing 1.2 × 10⁵ cells, in their right eye, and normal saline in left at p12. Five ROP rats received 12.5 mg/kg melatonin orally for five days (p12 to p17). Optical coherence tomography (OCT) and electroretinography (ERG) were performed on p47. Eyes were then harvested on p47, and after six months for histology, immunofluorescence (anti-calbindin, anti-PKC, and anti-Brn3), and immunohistochemistry (synaptophysin).

Results: Cell therapy alone and with melatonin increased retinal thickness, and improved oscillatory potentials on ERG. Combination therapy increased horizontal and retinal ganglion cell populations. All treatments improved synaptic maturity in the inner plexiform layer, but only combination therapy was effective on the outer plexiform layer.

Conclusion: Melatonin and BMMNCs combination therapy effectively ameliorates retinal structural and functional deficits at later ROP stages, without causing severe adverse effects. It significantly increases the survival of post-receptor retinal neurons and preserves retinal synaptic structures in the long term, highlighting the promising potential of this novel combination therapy approach to minimize visual deficits in ROP patients.