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Physiology of Ageing
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
There is a continual loss of neuronal tissue with advancing age. The brain weight may decrease by 6%–7% between 20 and 80 years of age. About 10,000 brain cells are lost per day from the age of 20 onwards. Lipofuscin accumulates in many nerve cells. The grey matter of the brain decreases from 45% to 35% of the total brain weight between the ages of 20 and 80 years (Figure 75.2).
The Injured Cell
Published in Jeremy R. Jass, Understanding Pathology, 2020
Lipofuscin is a golden brown ‘wear and tear’ pigment found in cells that are permanent (neurons and cardiac muscle) or stable (liver). This is a normal cell constituent and the amount increases with age. It is often more marked in organs showing atrophy. Lipofuscin is derived from partially degraded cell membranes and is contained within autophagic vacuoles.
Cell structure, function and adaptation
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Further evidence that genetic control of ageing occurs comes from developmental genetic studies in the nematode Caenorhabditis elegans in which mutations of a gene called clk-1 (the ‘clock’ gene) result in elongation of lifespan. Although homologues of these genes in primitive organisms may exist in humans, it is true that wear and tear is a major factor in ageing. Oxidative metabolism generates free radicals and over time these cause progressive damage to cell membranes, DNA, the cytoskeleton, and enzymes. Damaged lipids accumulate in cells in the form of lipofuscin, a giveaway sign of cellular ageing and damage. Although protective mechanisms exist to repair DNA and to remove damaged protein and oxidized lipid, there is gradual attrition over time that eventually leads to the cell's demise.
Secretory autophagy: a turn key for understanding AMD pathology and developing new therapeutic targets?
Published in Expert Opinion on Therapeutic Targets, 2022
Janusz Blasiak, Kai Kaarniranta
Normal functioning of the retina and vision maintenance require a continuous degradation of the used photoreceptor outer segments (POS) due to phagocytosis by RPE cells [54]. Impairment of this process leads to the accumulation of lipofuscin containing lipid-protein complexes derived mainly from oxidized unsaturated fatty acids and tiny amounts of saccharides and metals [55]. Lipofuscin may cause loss of lysosomal function due to inhibition of v-ATPase, oxidative damage, and/or lysosomal membrane permeabilization [51]. The main metal present in RPE lipofuscin is iron, and it was shown that disturbed iron homeostasis contributed to AMD pathogenesis [56,57]. Lipofuscin may exert its cytotoxic effect through its involvement in cellular senescence, another important effect in AMD pathogenesis [58]. Lipofuscin production may be stimulated by impaired mitochondria, important in AMD pathogenesis [59].
The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage
Published in Current Eye Research, 2021
Gökhan Koca, Evin Singar, Aylin Akbulut, Nuray Yazihan, Nihat Yumuşak, Ayten Demir, Meliha Korkmaz
The differences between the cells were determined semi-quantitatively under 200 magnification by choosing 10 random microscopic areas. Fibrosis was graded as 0 when it is absent; as 1 when it is focal and within 1 lobule; as 2 when it is less than 50% of the lobules; as 3 when it is diffuse in more than 50% of the lobules. The evaluation of inflammatory cells was determined by taking into consideration the inflammation density in each microscope field. In the evaluation of hyperemia, vessels dilated and lumen filled with erythrocytes were considered as hyperemia. Lipofuscin-like accumulation was defined as the number of cells with age-related pigments accumulated per lobule. The presence of lipofuscin was graded as 0 when absent, grade 1 as very few, grade 2 as less than 50%, and grade 3 as more than 50% of the gland. In nucleus changes and vacuolization, the numeric values were graded as 0 when it is between 0 and 3; as 1 when it is less than or equal to 20 cells with cellular changes; as 2 when it is between 21 and 50 cells with cellular changes; as 3 when it is more than 50 with cellular changes.
Retinal and Choroidal Changes of Vitreoretinal Lymphoma from Active to Remission Phase after Intravitreal Rituximab
Published in Ocular Immunology and Inflammation, 2020
Maria Vittoria Cicinelli, Alessandro Marchese, Elisabetta Miserocchi, Chiara Giuffré, Luigi Berchicci, Giuseppe Querques, Francesco Bandello, Giulio Maria Modorati
The present study disclosed the usefulness of UWF, both pseudo-color and FAF in monitoring the changes of eyes with VRL from the active to the remission phase. Retinal and RPE infiltrates often extend beyond the main vascular arcades and vitreitis localizes in the extreme periphery, leaving at the posterior pole the appearance to be clear. UWF imaging is more suitable to record these changes and their reduction in response to IVR treatment. Retinal and RPE infiltrates were more noticeable on UWF FAF than on pseudo-color, appearing as a granular pattern of alternating hyper-autofluorescent and hypo-autofluorescent spots.26 Hypo-autofluorescence indicates the absence of photoreceptors, RPE atrophy, or presence of intraretinal or subretinal lymphomatous infiltration that block the normal FAF signal from the RPE.7,27 Conversely, hyper-autofluorescence is correlated with impairment with the metabolism of the lipofuscin at the RPE level and accumulation of lipofuscin-derived debris. We have noticed a progressive reduction mainly in the hyper-autofluorescent component of the mottled FAF pattern of VRL. UWF was also useful to assess vitreitis, as previously described.28 We observed a meaningful improvement of the vitreous haze after IVR.