The prevalence of retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, has been increasing globally and is linked to the aging population and improved life expectancy. These diseases are characterized by chronic, progressive neuronal damage or depletion of the photoreceptor cells in the retina, and limited effective treatment options are currently available. Mesenchymal stem cell-derived exosomes (MSC-EXOs) containing cytokines, growth factors, lipids, mRNA, and miRNA, which act as mediators of intercellular communication transferring bioactive molecules to recipient cells, offer an appealing, non-cellular nanotherapeutic approach for retinal degenerative diseases. However, treatment specificity is compromised due to their high heterogeneity in size, content, functional effects, and parental cellular source. To improve this, engineered MSC-EXOs with increased drug-loading capacity, targeting ability, and resistance to bodily degradation and elimination have been developed. This review summarizes the recent advances in miRNAs of MSC-EXOs as a treatment for retinal degeneration, discussing the strategies and methods for engineering therapeutic MSC-EXOs. Notably, to address the single functional role of engineered MSC-EXOs, we propose a novel concept called "Compound Engineered MSC-EXOs (Co-E-MSC-EXOs)" along with its derived potential therapeutic approaches. The advantages and challenges of employing Co-E-MSC-EXOs for retinal degeneration in clinical applications, as well as the strategies and issues related to them, are also highlighted.

Macrophage migration inhibitory factor (MIF), a multifunctional cytokine, is secreted by various cells and participates in inflammatory reactions, including innate and adaptive immunity. There are some evidences that MIF is involved in many vitreoretinal diseases. For example, MIF can exacerbate many types of uveitis; measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment. MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage. Furthermore, MIF is critical for retinal/choroidal neovascularization, especially complex neovascularization. MIF exacerbates retinal degeneration; thus, anti-MIF therapy may help to mitigate retinal degeneration. MIF protects uveal melanoma from attacks by natural killer cells. The mechanism underlying the effects of MIF in these diseases has been demonstrated: it binds to cluster of differentiation 74, inhibits the c-Jun N-terminal kinase pathway, and triggers mitogen-activated protein kinases, extracellular signal-regulated kinase-1/2, and the phosphoinositide-3-kinase/Akt pathway. MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway. This review focuses on the structure and function of MIF and its receptors, including the effects of MIF on uveal inflammation, retinal degeneration, optic neuropathy, retinal/choroidal neovascularization, and uveal melanoma.

In ophthalmic surgery, particularly in procedures involving the posterior segment, clinicians face significant challenges in maintaining precise control of hand-held instruments without damaging the fundus tissue. Typical targets of this type of surgery are the internal limiting membrane (ILM) and the epiretinal membrane (ERM) which have an average thickness of only 60 $\mu \rm{m}$ and 2 $\mu \rm{m}$ , respectively, making it challenging, even for experienced clinicians utilising dedicated ophthalmic surgical robots, to peel these delicate membranes successfully without damaging the healthy tissue. Minimal intra-operative motion errors when driving both hand-held and robotic-assisted surgical tools may result in significant stress on the delicate tissue of the fundus, potentially causing irreversible damage to the eye. To address these issues, this work proposes an intra-operative vision-and-force-based compliance control method for a posterior segment ophthalmic surgical robot. This method aims to achieve compliance control of the surgical instrument in contact with the tissue to minimise the risk of tissue damage. In this work we demonstrate that we can achieve a maximum motion error for the end effector (EE) of our ophthalmic robot of just 8 $\mu \rm{m}$ , resulting in a 64 $\%$ increase in motion accuracy compared to our previous work where the system was firstly introduced. The results of the proposed compliance control demonstrate consistent performance in the force range of 40 $\rm{mN}$ during membrane tearing.