A pitfall in the clinical process is not that a theory could be false, but that it is taken for granted when it appears rational and not challenged with brand-new experiments,” said Ali Hafezi-Moghadam, MD, PhD, director of the Molecular Biomarkers Nano-Imaging Laboratory (MBNI) in the Department of Radiology at the Brigham and an associate teacher at Harvard Medical School. “The evidence we have collected here calls the long-believed theory about diabetic cataracts into question, begging us to reexamine the existing dogma that has been depended on for discussing diabetes-associated cataracts.”
The current hypothesis behind diabetic cataract development is coined “the sugar hypothesis” and suggests that high blood sugar– a hallmark of diabetes– precedes cataract advancement. The working presumptions underlying the sugar hypothesis explain greater levels of glucose in the lenses of individuals with diabetes convert to a sugar alcohol molecule called sorbitol, which induces structural modifications to the lens of the eye that precede cataract advancement.
Immune cell trafficking in diabetic cataract development. (A) Novel in situ visualization strategy for studies of immune cell trafficking in the eye. (B) Immune cell passing through ciliary bodys epithelial cells. (C) Microstructural lesions in the early phases of diabetic cataract development. Credit: Images provided by Hafezi-Moghadam et al
. Hafezi-Moghadam and colleagues studied the Nile lawn rat, a design that they originally reported spontaneously establishes type 2 diabetes when kept in captivity and carefully simulates the condition in humans. Similar to humans with type 2 diabetes, these animals initially develop insulin resistance and high blood insulin levels before their blood glucose rises above regular. Utilizing a specialized strategy termed stereo microscopy with double bright-field lighting, scientists observed the advancement of dot-like microlesions, which inclined cataract formation, in the inner cortical regions of the lens. Suddenly, they saw that in nearly half of the animals evaluated, these microlesions appeared before the animals established hyperglycemia, or high blood glucose, suggesting that it was not raised blood sugar levels themselves causing cataract development.
In these locations, where the immune cells traversed the pill of the lens, they discovered that the epithelial cells that generally cover the inner surface area of the lens pill changed their identity and behaved in a different way. These modifications, likewise referred to as epithelial-mesenchymal transformation (EMT), were followed by seemingly unorganized cell growth, cell death, and cell migrations into the body of the lens.
While still prematurely to inform just what causes the epithelial cells and immune cells to behave the method they do, the scientists conclude that their research study prompts more investigation of prevailing theories. It might likewise bring the medical neighborhood an action better to comprehending the cellular mechanisms underlying the origins of diabetic problems during the pre-diabetic stage of the disease. And as soon as we understand the pathogenesis, Hafezi-Moghadam imagines, we can start to browse for how to avoid individuals with diabetes from establishing cataracts and potentially other issues somewhere else in the body.
” While cataracts today are quickly detachable with surgical treatment, this treatment features the danger of complications and is costly, both for people and our health care system,” stated Hafezi-Moghadam. “With over 500 million people around the world and 37 million Americans having diabetes, the excellent bulk of whom have type 2, there is a reward for searching for non-surgical methods of avoiding, slowing, and even reversing this complication. Perhaps one day it will become possible to prevent performing these surgeries completely. Which needs that we return to the fundamentals of the cellular procedures underlying cataract advancement.”
Reference: “Pre-hyperglycemia immune cell trafficking underlies subclinical diabetic cataractogenesis” by Ehsan Ranaei Pirmardan, Yuanlin Zhang, Aliaa Barakat, Marzieh Naseri, Christoph Russmann and Ali Hafezi-Moghadam, 24 January 2023, Journal of Biomedical Science.DOI: 10.1186/ s12929-023-00895-6.
Funding: This work was supported by NIH Impact Award (DK108238-01, AHM), and JDRF Innovation Award (INO-2016-222-A-N, AHM).
New findings challenge the “sugar hypothesis” in diabetic cataracts, exposing that immune cells trigger cellular changes in the eye lens in the past high blood glucose levels take place. This suggests diabetic problems may start during the pre-diabetic state and calls for a reevaluation of existing theories.
In preclinical designs, private investigators discovered a novel mechanism underlying the development of diabetic cataracts that weakens present hypothesis.
Their research study exposed that immune cells migrate from the eyes ciliary bodies towards the lens, resulting in cellular changes that jeopardize lens function. These changes happen even in the past high blood sugar levels are present, suggesting that diabetic complications might begin during the pre-diabetic state.
New findings from private investigators at Brigham and Womens Hospital, a founding member of the Mass General Brigham health care system, contradict previous notions about sugars role in the onset of diabetic cataracts. Using an animal design that more carefully recapitulates type 2 diabetes in humans, the research team discovered early signs of damage in the eye before the start of type 2 diabetes, suggesting that diabetic complications may begin throughout the pre-diabetic state. Outcomes are published in the Journal of Biomedical Science.
New findings from detectives at Brigham and Womens Hospital, an establishing member of the Mass General Brigham healthcare system, oppose previous ideas about sugars function in the beginning of diabetic cataracts. The current hypothesis behind diabetic cataract advancement is created “the sugar hypothesis” and suggests that high blood sugar– a trademark of diabetes– precedes cataract development. The working presumptions underlying the sugar hypothesis explain higher levels of glucose in the lenses of individuals with diabetes transform to a sugar alcohol molecule called sorbitol, which causes structural changes to the lens of the eye that precede cataract advancement. Immune cell trafficking in diabetic cataract development. (C) Microstructural lesions in the early phases of diabetic cataract development.
