## 1 Introduction  
Diabetic retinopathy (DR) remains a significant impediment to diabetes and a primary source of blindness and vision loss in adults. With an increasing worldwide prevalence of diabetes, which is predicted to be 700 million by 2045, the suffering of DR on both people and the burden on the healthcare system is projected to be extremely high [1, 2]. Despite significant laboratory and clinical investigations, the primary etiology of diabetes-related vision loss and blindness remains unknown. The rising prevalence of diabetes demands new approaches to understanding the disease's pathogenesis to enhance retinopathy's early detection, prevention, and treatment. In recent decades, many functional tests and molecular data have demonstrated early neurodegeneration in the diabetic retina, which might contribute to microvascular damage, the classical hallmark of DR [3, 4, 5]. The precise cause(s) of early retinal neurons injury in diabetes are not known. Although numerous reports established that diabetes increases apoptosis and oxidative stress, while decreasing neurotrophic factors, interestingly, all of these are critical markers of neurodegeneration in the diabetic retina [3, 6, 7, 8, 9, 10].  
Both retinal nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are known to aid in the preservation and endurance of vascular and neuronal cells (BDNF) [11, 12, 13]. Alternatively, diabetes-induced changes in these neurotrophic factors are connected to the pathogenesis of diabetic retinopathy [14, 15]. Downregulation of neurotrophins or alterations in their signaling (BDNF-TrkB-Akt) could significantly change retinal and brain function [16, 17]. Previously, several researchers reported lower levels of NGF and BDNF in diabetic rodent retinas [18, 19, 20]. Another central process that leads to retinal cell death in diabetes is apoptosis, which is mainly increased due to high oxidative stress. Increased oxidative stress as in the case of diabetes disrupts the mitochondrial membrane, causing an imbalance of apoptotic molecules. As a result, cytosolic pro-apoptotic Bax is translocated to the mitochondria to release cytochrome c, further escalating the apoptotic process. Anti-apoptotic Bcl-2 proteins, which regulate this process, are found to be altered in diabetic retinas [21]. Thus, targeting apoptosis as a preventive or therapeutic strategy would be an ideal approach. Several studies reported treatments to diabetic rodents with flavonoids including rutin-, hespertin- and quercetin-suppressed apoptosis and improved apoptotic regulatory proteins in the retina [8, 19, 22, 23].  
_L. regularis_ is a traditional herbal plant from the Loranthaceae family primarily found in Yemen and Saudi Arabia. Mistletoes are members of the Loranthaceae family which are often used to treat hypertension, diabetes, and inflammatory disorders [24, 25, 26]. Previous studies reported that the active components of _L. regularis_ served as antioxidant, antimicrobial, and anti-inflammatory factors [27, 28]. More recently, our research team has investigated the potential beneficial effects of _L. regularis_ against inflammation and oxidative stress in diabetes-induced hepatocellular damage and nephropathy [29, 30]. _L. regularis_ and its constituents, being bioactive with a potentially beneficial role in combating diabetes and its complications, here we used oral treatments of this plant extract to protect neurodegenerative factors in the retina of STZ-induced rats.  
This study aimed to employ extracts of _Loranthus regularis_ (_L. regularis_) to ameliorate altered neurotrophic factors, apoptotic factors, and oxidative stress in diabetic retinas, which might ameliorate neurodegeneration. Interestingly, our study suggests the beneficial effects of oral treatments of _L. regularis_ to diabetic rat retinas by ameliorating diminished neurotrophic effects and reducing oxidative stress, and apoptosis, which may protect retinal neurodegeneration early in diabetes.