Great to so you @bwjones.bsky.social. Beer in Denver ?

I defended my PhD 10 years ago today. That was the least remarkable thing that happened that day. Sharing something I wrote about it last year. Since then "the horrors persist but so do we." And with dignity.

50 day free link nam11.safelinks.protection.outlook.com?url=https%3A...

Thank you @brainimmunity.bsky.social !

Bonus 3/3
we provide a marker list in table format. Spoil alert - no, there is no one marker to discern monocyte derived macrophages versus microglia in the retina

Bonus 2/3
We review the functional roles of eye RTMs in health and disease, including a synthesis in table form

Bonus 1/3 (for Blusky only!)
We argue for sunsetting the M1/M2 dichotomy in eye macrophage research, supported by single cell RNA-seq data demonstrating a complexity that does not conform to this binary framework

this work would not have been possible without my incredible co-authors: Eden Jacob,
Seth Fortmann, Kyoung Woo Kim, Drew Voigt, Maria Grant, Dan Stamer, Katy Liu, Jeremy Lavine, and Peter Wieghofer.

Principles of resident tissue macrophages revealed by the eye Macrophages are no longer viewed as transient immune passersby but as integral tissue components that regulate physiological homeostasis. Many residen…

So the question is not only: where do resident macrophages come from? It is also: when does self-maintenance become durable, and when does it fail to do so? That is the problem Establishment Kinetics is meant to solve. Full paper in Advances in Immunology www.sciencedirect.com/science/chap... 10/11

From this intra-organ comparison, three broader principles emerge:
1️⃣ Establishment timing ≠ equilibrium density
2️⃣ RTM identity ≠ lifelong durability
3️⃣ Anatomical proximity + immune privilege ≠ kinetic class
9/11

Eye mac populations separated by submillimeter distances can follow radically different trajectories. That makes it possible to distinguish true determinants of durability from simple correlates like anatomy, vascularity, or immune privilege. 8/11

Why the eye? It provides a natural experiment. Multiple macrophage populations coexist within a single organ under shared systemic conditions, yet differ sharply in long-term maintenance. That lets us compare persistence without the confounders inherent to brain vs lung vs skin comparisons. 7/11

Four kinetic classes:
🔵 Permanent: early acquisition, lifelong maintenance
🔵 Juvenile-Established: early attrition, then durable equilibrium
🔵 Adult-Established: continued attrition into adulthood, then late stabilization
🔵 Time-Limited: progressive attrition without durable equilibrium
6/11

We propose Establishment Kinetics: not just who enters a niche, but when, or whether, macrophage pops acquire durable autonomous self-maintenance under physiological conditions. We argue this capacity is macrophage-intrinsic, while tissue context stabilizes, delays, or progressively erodes it. 5/11

This is where the anomalies appear. A closed-niche logic fits microglia. But permanence also occurs e.g. in Langerhans cells and Kupffer cells. And competition can shape equilibrium abundance without explaining whether self-maintenance actually stabilizes. 4/11

Mac-dependent tissue functions require long-term residence. A population can seed a tissue, acquire residency, and specialized functions, yet fail to persist across life. The key question is not just how macrophages enter tissues, but whether they achieve durable self-maintenance once there. 3/11

Current frameworks explain a lot through #ontogeny, niche accessibility, competition, #monocyte replacement, and time in tissue. But they do not fully explain whether self-maintenance becomes a durable population-level property under physiological conditions. 2/11

Resident tissue #macrophages (RTM) are now recognized as integral regulators of tissue physiology, not transient immune sentinels. one fundamental question remains unresolved: why do some populations achieve lifelong self-maintenance, while others are replaced under steady-state conditions? 🧵1/11

Long-lived resident tissue macrophages govern intraocular pressure homeostasis by regulating extracellular matrix turnover, contributing to resistance-generating tissues that are dysfunctional in glaucoma @cp-immunity.bsky.social
www.cell.com/immunity/ful... @dukeeyecenter.bsky.social

Thank you @payalyokota.bsky.social !

Huge thanks to all the authors, and of course the National Eye Institute for funding this important consortium!

link:papers.ssrn.com/sol3/papers.cfm

This coordinated approach transforms isolated findings into comprehensive mechanistic frameworks, demonstrating how technological convergence combined with collaborative science accelerates discovery and establishes foundations for understanding ocular surface circuitry in health and disease.

The roadmap progresses through 3 phases: standardizing methodological foundations; achieving technological convergence through multi-modal synthesis; and advancing clinical translation via cross-species harmonization, therapeutic target identification, and patient characterization strategies.

Thru a multi-institutional collaboration, the consortium roadmap systematically integrates four complementary pillars: retrograde labeling; omics technologies; animal models; and research models and human clinical imaging.

Preprint of National Eye Institute, U01-Funded Consortium Consensus on Ocular Surface Innervation is out ! "Corneal Innervation Research at a Crossroads: A Tool-Driven Roadmap for the Future "

Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina - Scientific Reports Scientific Reports - Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina

#2016Nostalgia when we published our first #microglia paper ! www.nature.com/articles/sre...

Surfers in Bondi Beach #Australia hold a tribute the victims of the attack last week. ❤️

I am excited to share our new paper @JExpMed led by our one and only #Alejandra_Aroca