Macular Degeneration is driven by inflammation

Dr. Weeks’ Comment: Age Related Macular Degeneration (both wet and dry) is a disease of the neurological system which is 100x more dense with omega 6 fatty acids than omega 3 fatty acids. (the skin is 1000x more omega 6 than omega 3) Therefore unadulterated omega 6 oils (not toxic rancid omega 6 vegetable oils) but rather unadulterated organic seed and nut oils are essential for eye health. If those omega 6 oils can be full of anti-inflammatory and anti-oxidant forces like this 3 seed drink, then we have a safe and powerful remedy.

Front Aging Neurosci. 2018; 10: 203. Published online 2018 Jul 5. doi: 

IGF-1, Inflammation and Retinal Degeneration: A Close Network

Ana I. Arroba,

Role of IGF-1 in retinal inflammation and degeneration

Neuroinflammation is currently considered as an early event in the pathophysiology of many neurodegenerative disorders because despite its essential role in protecting tissues during the early steps of disease, the continuous presence of proinflammatory stimuli induces cellular damage (Glass et al., 2010; Arroba et al., 2016a; Arroba and Valverde, 2017). It is widely accepted that in the central nervous system (CNS) astrocytes and microglia are the cells that play a critical role in neuroinflammation that precedes the neurodegenerative diseases (Cherry et al., 2014; Arroba et al., 2016a). In this scenario, activated microglia and reactive astrocytes participate into the release of different inflammatory mediators including cytokines, chemokines, reactive oxygen species (ROS), and nitric oxide (NO), all of them contributing to the maintenance of a chronic neuroinflammatory milieu that ultimately may be responsible of neurotoxic damage in the CNS (Cuenca et al., 2014).

Insulin-like growth factor-I (IGF-1) is the ligand of the IGF-1 receptor (IGF-1R) which belongs to the tyrosine kinase receptor superfamily and regulates normal developmental growth through endocrine and autocrine/paracrine-mediated mechanisms (Bates et al., 1995). IGF-1 is also a potent survival factor for many tissues (Heemskerk et al., 1999). Particularly, IGF-1 is a neurotrophic peptide in the CNS where it promotes synaptic plasticity, enhances nerve growth and triggers antiapoptotic-mediated signaling cascades (Carro et al., 2003). All these IGF-1 functions are critical for the protection of nerve cells against neurodegenerative processes (Varela-Nieto et al., 2013; Yamamoto et al., 2014). Deficiency in the IGF1gene in humans is related with neuronal disorders such as microcephaly, mental retardation, and bilateral sensorineural deafness (Woods et al., 1996; Walenkamp et al., 2005; Netchine et al., 2009).

In several pathologies such as type 1 diabetes mellitus (T1DM) antiinflammatory properties have been attributed to the IGF-1/IGF-IR system in the CNS by counteracting the inflammatory milieu triggered by microglial activation in the hypothalamus (Zhang et al., 2016). However, controversial effects of this peptide have been described regarding its proinflammatory effect in other pathological contexts. In a recent study, IGF-1 was overexpressed in hepatic stellate cells of mice deficient in the Abcb4 gene, a preclinical model for chronic cholangiopathy. The authors of this work found a higher stimulation of the fibrogenic processes in these double mutant mice which was accompanied by the increased expression of proinflammatory markers together with the presence of infiltrating macrophages in the liver (Sokolovic et al., 2013). Regarding this duality of IGF-1 effects in inflammation, a recent study in zebrafish has evidenced that growth factors including IGF-1 and insulin together with cytokines activate common signaling pathways that are necessary for the reprogramming of Müller glial cells and retinal regeneration upon injury (Wan et al., 2014).

The retina has been considered as a projection of the CNS and, in this tissue, neuroinflammatory processes occur in a similar way as in the brain. In fact, retina and brain share similarities due to their common neuroectodermal origin and derivation from the anterior neural tube and, therefore, both tissues respond similarly to the proinflammatory insults. Based on that, it is conceivable to integrate the retina as a part of the brain (MacCormick et al., 2015).

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