A study from @ucleye.bsky.social has identified a key #protein that triggers diabetic retinopathy. The protein LRG1 is the cause of the early damage and targeting this could offer a way to protect vision. #Ophthalmology
www.science.org/doi/10.1126/...

Time for my weekly post, and today I report on some exciting new research from my lab. Especially for any diabetics out there.

Important News from the World of Diabetes
open.substack.com/pub/stephene...

A key protein has been identified as an early trigger of diabetic retinopathy, offering a potential new approach to prevent vision loss in people with diabetes before significant damage occurs. doi.org/g97skc

A team led by Dr @giuliaderossi.bsky.social @ucleye.bsky.social has identified a key protein that triggers diabetic retinopathy – a leading cause of sight loss among working-age adults – in a finding that has the potential to revolutionise how the disease is treated

A study led by @giuliaderossi.bsky.social has identified a key protein that triggers diabetic retinopathy, a leading cause of blindness. The study, funded by @diabetesuk.bsky.social is published today and featured on the cover of #ScienceTranslationalMedicine.
www.ucl.ac.uk/news/2025/oc...

So amazing to see our work on the cover of Science Translational Medicine!!

The new issue of #ScienceTranslationalMedicine is out now!

Mass production of regulatory T cells treats autoimmune disorders in mice, a preclinical study uncovers a promising therapeutic target in diabetic retinopathy, and more. https://scim.ag/3WeFm1R

@ucl.ac.uk scientists discover early trigger of diabetic eye disease, paving the way for new sight-saving treatments. The TRO is proud to support research projects like this by working closely with our academics and see the impactful work progressing for patient benefits. 
Full story: bit.ly/3Lo0vEk

Leucine-rich α-2-glycoprotein 1 initiates the onset of diabetic retinopathy in mice | Science Translational Medicine www.science.org/doi/10.1126/...
Our latest publication regarding LRG1. Congratulations to Dr De Rossi for her immense contribution. So proud to have made a significant contribution.

None of this would have been possible without the generous support of @diabetesuk.bsky.social, #moorfieldseyecharity, @ucltro.bsky.social and @wellcometrust.bsky.social 🙏

Also very grateful to
@ucleye.bsky.social
for being such an inspiring and supportive place to do science. 🧪

Grateful to @greenwoodjohn.bsky.social and
@stephenemoss.bsky.social
for co-leading this study with such insight and enthusiasm, and to all co-authors for their invaluable contributions.

Finally — and most importantly —
a single intravitreal injection of an LRG1-blocking antibody (15C4) significantly reduced all early vascular defects and restored visual function in diabetic mice.
🎯A potential early therapeutic strategy for preventing vision loss. 👁️

Although these vascular changes appear subtle, computational modelling revealed that they markedly impair retinal oxygenation, providing a mechanistic explanation for the reduced ERG responses seen in diabetic eyes.

This LRG1-driven pericyte dysfunction leads to pathological microvascular remodelling. We see decreased capillary density and diameter. Interestingly, this is also seen in human DR patients at high risk of progressing to the advanced stage (Nicholson et al. JAMA 2019).

Once secreted, LRG1 acts on pericytes through TGFbeta signalling, driving them toward a more contractile and fibrotic phenotype.
We observed increased myosin light chain activation and thickened basement membrane in diabetic wild-type mice, but not in those lacking Lrg1.

So we moved to diabetic mice to investigate the source and the impact of excessive LRG1 production in diabetic retinas.

We found that the inflamed retinal endothelium is the main source of LRG1 and that retinal Lrg1 expression is switched on months earlier than that of Vegf.

We found that LRG1 is increased in retinas from people with diabetes and DR, corroborating several cross-sectional proteomic studies showing correlation between plasma and vitreous LRG1 with the duration of diabetes.

We identified leucine-rich α-2-glycoprotein 1 (LRG1) as an initiator of early microvascular dysfunction in the diabetic retina and show that blocking LRG1 in mouse models of diabetes protects them from developing DR. www.science.org/doi/10.1126/...

📢Our new paper is out in
@science.org #ScienceTranslationalMedicine
📢

Diabetic retinopathy (DR) is a leading cause of blindness. Patients show vascular changes in their retinas long before vision starts to deteriorate.
What triggers these early defects? Could targeting them prevent vision loss? 🧵

And so it begins! 🎓 Emily’s PhD journey into shedding light on the fibrotic response in wet AMD. Huge thanks to @macularsociety.org for supporting this talented young scientist, and to @amandajcarr.bsky.social for co-supervising! 👏✨

What an absolute pleasure it’s been to host Precious in my lab these past few weeks! Honoured to play a small part in what I’m sure will be a stellar career.

Huge thanks @diabetesuk.bsky.social and Windsor Fellowship for funding her internship.